• Users Online: 154
  • Home
  • Print this page
  • Email this page

 Table of Contents  
REVIEW
Year : 2021  |  Volume : 11  |  Issue : 2  |  Page : 72-82

A review on the neuroprotective effects of hyperbaric oxygen therapy


Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

Date of Submission23-May-2020
Date of Decision27-May-2020
Date of Acceptance11-Jun-2020
Date of Web Publication26-Mar-2021

Correspondence Address:
Ali Reza Khalatbary
Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2045-9912.311498

Rights and Permissions
  Abstract 


Hyperbaric oxygen therapy, intermittent breathing of 100% oxygen at a pressure upper than sea level, has been shown to be some of the neuroprotective effects and used therapeutically in a wide range of neurological disorders. This review summarizes current knowledge about the neuroprotective effects of hyperbaric oxygen therapy with their molecular mechanisms in different models of neurological disorders.

Keywords: apoptosis; clinical trial; hyperbaric oxygen; inflammation; in vitro; in vivo; neuroprotection; oxidative stress


How to cite this article:
Ahmadi F, Khalatbary AR. A review on the neuroprotective effects of hyperbaric oxygen therapy. Med Gas Res 2021;11:72-82

How to cite this URL:
Ahmadi F, Khalatbary AR. A review on the neuroprotective effects of hyperbaric oxygen therapy. Med Gas Res [serial online] 2021 [cited 2021 Apr 16];11:72-82. Available from: https://www.medgasres.com/text.asp?2021/11/2/72/311498




  Introduction Top


Nervous system diseases are one of the leading causes of death and disability worldwide due to the limitation of effective treatment strategies. Although some promising strategies have been reported in the animal models of nerves system disorders, they often fail to work in clinical practice.Therefore, new treatment strategies need to be developed and exploited. Within the previous decades, various pharmaceutical compounds as well as various therapeutic methods with neuroprotective effects have been described, including high pressure oxygen therapy as a nondrug and noninvasive therapy. Hyperbaric oxygen (HBO) therapy (HBOT) is defined as the intermittent breathing of pure oxygen inside a hyperbaric chamber at a pressure above sea level. During HBOT, the amount of dissolved oxygen in the plasma as well as saturated hemoglobin with oxygen increases, leading to greater oxygen availability to the organs.[1],[2] It is well documented that HBOT has neuroprotective effects against experimental spinal cord injury (SCI),[3] brain injury,[4],[5] neurodegenerative disease,[6],[7] peripheral nerve injury,[8],[9] and neurotoxicity models of rodents.[10] On the other hand, clinical evidence to support the neuroprotective properties of HBOT is limited.[11] In regard to the neuroprotective effects of HBOT, accumulating evidence indicates an association between the beneficial effects to a variety of biological properties mainly anti-oxidative,[12] anti-inflammatory,[13] and anti-apoptotic properties,[14] in addition to improvement of oxygen supply and neural metabolism.[15],[16] This paper presents an up-to-date review of the neuroprotective effects of HBOT with its molecular mechanisms in different models of neurological disorders in three parts.


  In Vivo Studies Top


A lot of in vivo experimental studies have been conducted on the HBOT neuroprotection and its underlying molecular mechanisms, summarized in Additional Tables 1–5.[Additional file 1]

SCI

SCI is a complex process that is first caused by primary mechanical trauma or ischemia and then continues by secondary damage caused by various mechanisms.[17] SCI outcome is related to the amount of secondary damage caused by a series of biochemical, molecular, and cellular cascades including, apoptosis, inflammatory reaction, and lipid peroxidation.[18],[19],[20],[21] In this regard, despite the report of Balentine[22] which indicates spinal cord gray matter necrosis and subsequent motor deficit following exposure to HBO (413.68 kPa on consecutive days) in rats, Higgins et al.[23] documented for the first time that HBOT during the early phases of SCI preserves the marginal spinal cord long tracts due to reduction of edema or reversal of focal hypoxia. HBOT shortly after spinal cord ischemia in rabbits (30 minutes after reperfusion) had protective effects through attenuation of the selective motor neuron death; however, delayed therapy (6 hours after reperfusion) with HBO did not change the prognosis.[24] Subsequent studies demonstrated that multiple HBOT (once daily for 1 week starting at 6 hours following injury) produced significantly more neurological improvements than the control group.[25],[26] Biochemical analysis of HBOT on the oxidative status after SCI revealed that HBO prevents oxidative damage to the spinal cord.[27] Another study to determine other mechanisms of neuroprotective effects of HBOT on experimental SCI showed that HBOT significantly attenuated SCI-induced interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) overproduction, and in turn significantly increased the number of both glial cell line-derived neurotrophic factor- and vascular endothelial growth factor (VEGF)-positive cells and spinal cord IL-10 production.[28] In regard to spinal cord tissue enzyme levels following HBOT, it was found that postoperative HBOT was useful in terms of biochemical parameters such as nitric oxide, glutathione peroxidase, superoxide dismutase (SOD), and nitric oxide synthase (NOS) activity rate in the damaged part of the spinal cord tissue following SCI.[29] HBOT decreases spinal cord edema, improves neuronal function, and stabilizes the blood-spinal cord barrier through downregulation of matrix metalloproteinase (MMP)-2, IL-6, and MMP-9 and upregulation of VEGF.[30] Another study documented that HBOT through inducible NOS (iNOS) mRNA-iNOS-nitric oxide signaling pathway can promote the neuroprotection following SCI.3 The inflammatory process is one of the major causes of secondary SCI. In this regard, Yang et al.[31] documented that HBO intervention reduced secondary SCI via nuclear factor-κB (NF-κB) and high-mobility group protein B1 (HMGB1) downregulation in rats with acute SCI. In regard to the other neuroprotective mechanism of HBO on SCI, it was documented that hypoxia-inducible factor-1α (HIF-1α) reduction and VEGF elevation by HBO intervention may be inversely associated with spinal cord repair.[32] Another study documented that HBOT via Toll-like receptor (TLR)2/NF-кB signaling induced protective effects against rat SCI.[33] The researchers believe that HBOT reduces secondary SCI and promotes neurological outcome through TLR2/NF-кB signaling pathway. A research has shown that early HBOT (at the 1st hour after trauma) contributed to the biochemical and histopathological improvement of the rats after SCI.[34] To determine the mechanisms of HBOT in SCI, a study measured the expression levels of connexin 43 and VEGF in the damaged part of the spinal cord.[35] The results showed that VEGF significantly increased, while the level of connexin 43 significantly decreased after HBOT. Immunoreactive responses are like a double-edged sword in which the macrophages were considered as predominant inflammatory cells. In this regard, results of a study showed that HBOT by altering the macrophage M1 phenotype to the M2 phenotype modified the inflammatory environment, which promotes functional recovery and axonal extension.[36] Liang et al.[37] demonstrated that HBOT compromised NACHT domain leucine rich repeat and pyrin domain containing protein 3 (NALP-3) inflammasome, caspase 1 and adaptor molecule apoptosis-associated speck-like protein, in addition to mitigating IL-1β release in the damaged spinal tissue. HBOT has a protective effect on SCI by reducing neuronal cell apoptosis and MMP-9/2 gene expression in rats, so that improved motor function scores and increased myelinated nerve fibers.[38] Studies emphasize the key role of endoplasmic reticulum stress in the induction of neuronal apoptosis following SCI. In this regard, it was documented that HBOT by inhibiting endoplasmic reticulum stress-induced apoptosis alleviated secondary SCI and thereby improved the neurological function.[39] Another study tested the hypothesis that HBOT via regulation of c-Jun N-terminal kinase (JNK) and glucose-regulated protein 78 expression ameliorates secondary SCI.[40] The results showed that HBOT increased glucose-regulated protein 78 level and decreased that of JNK which leads to tissue and motor recovery. In regard to the HBOT effects on inflammatory process after SCI, Kang et al.[41] documented that HBO intervention by regulation of NF-κB, TLR4, and HMGB1 signaling pathways reduces secondary SCI in rats. Autophagy, a lysosome mediated metabolic pathway, plays a key role in cell survival, differentiation, development, and homeostasis. It has been reported that regulation of autophagy improves neurological function after SCI.[42] In this regard, it was documented that enhancement of autophagy expression and acceleration of cell repair rate after SCI may be another mechanism of action of HBOT.[43] HBOT potentially by inhibiting receptor expression for monocyte chemoattractant protein 1 and advanced glycation end products recovers locomotor function.[44] Results of another study which was investigated the mechanisms of HBOT following SCI, suggested that reducing lipid oxidation and oxygen free radicals is one of the mechanisms.[45] Sun et al.[46] documented that HBO significantly improved the recovery of neuronal function and fractional anisotropy compared to SCI group on days 7, 14, and 21 after SCI. Recently, it was documented that HBOT improves neurological disorders by amelioration of apoptosis and suppressing dendritic/synaptic degeneration through upregulating the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B signaling pathways in the anterior horn of spinal cord after SCI.[47] Also, another study revealed that HBO via stromal cell-derived factor-1/CXC chemokine receptor 4 axis activation and promotion of BDNF expression improves neurological function after SCI in rats.[48] HBO improves functional recovery through inhibiting iNOS, cyclooxygenase-2, glial fibrillary acidic protein, and neuron-glial antigen 2; meanwhile this process may be due to inhibition of NF-κB and Akt pathways.[49] Assessment of HBOT in rat model of SCI using diffusion tensor imaging showed that HBOT for 4 weeks is the more appropriate course.[50]

Brain injury

Studies have shown that brain damages after stroke or trauma are due to a variety of pathophysiological processes such as nitrative and oxidative stress, disruption of the blood-brain barrier (BBB), excitotoxicity, neural cell death, inflammatory reactions, and deficits in angiogenesis.[51],[52],[53] In this regard, Weinstein et al.[54] showed that HBOT conferred significant protection against death from untreated cerebral ischemia in anaesthetized gerbils, while histological examination showed that the extent of patchy bilateral ischemic neuronal damage was much less in surviving gerbils that received HBOT. After that, a study was conducted to determine the effects of HBOT on free radical generation and lipid peroxidation following global cerebral ischemia.[55] Results of this study showed that HBOT elevated the level of oxygen free radicals after ischemia in the brain, but, this elevation was not accompanied with increased lipid peroxidation or decreased neurophysiological recovery. In fact, despite the initial increase in free radical generation, the amount of peroxidation was similar to control group, while the cortical somatosensory evoked potential recovery was more than 50-fold in the HBO-treated animals relative to the control group. Another study documented that HBO reduces blood flow and brain vascular permeability after global cerebral ischemia in rabbits, however, recovery of the somatosensory evoked potential was the same as control and HBO groups.[56] While, HBOT in another study had no beneficial effects on neurologic outcome after acute focal cerebral ischemia.[57] It was reported that adult rats with middle cerebral artery occlusion which are exposed to HBO immediately or after a 60-minute delay showed improvement in motor impairment, as well as a reduced cerebral infarction compared to normal atmospheric pressure.[58] Assessment of the role of neutrophils and prophylactic HBO on cerebral injury revealed that HBOT before ischemia at 2.8 atmosphere absolute (ATA; 1 ATA = 101.325 kPa) for 45 minutes reduces myeloperoxidase concentration, functional neurologic deficits, and cerebral infarct volume through inhibiting neutrophil sequestration.[59] Results of an investigation revealed that altered excitatory amino acids and brain energy metabolites which occurred during brain ischemia were regulated with HBOT at different times after ischemia.[60] Neurotrophin-3 plays a protective role against neuronal cell death in response to brain ischemia. In this regard, it was documented that HBOT decreases downregulation of the post-ischemic neurotrophin-3 mRNA in the rat hippocampus.[61] HBOT has dual effect on cerebral infarction, and using HBO within 6 hours of ischemia-reperfusion injury can be beneficial but using HBO 12 hours or more after injury can be harmful, while tissue damage was not reduced by HBO during 4 hours of permanent focal cerebral ischemia.[62] Yin et al.[63] revealed that HBOT can lead to an inhibition of cyclooxygenase-2 over-expression in cerebral cortex after cerebral ischemia. Hyperbaric oxygenation reduces focal brain damage and reduces striatal dopamine secretion after occlusion of middle cerebral artery.[64] One of the molecular mechanisms of protection by HBO is the prevention of apoptosis which might preserve more tissue in the brain and improve neurological function. In this regard, Yin et al.[65] documented that HBOT (7 days after reperfusion) reduced brain infarction and improved neurologic scores by preventing apoptotic death (abolished DNA fragmentation and reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cell number) in rat ischemic cortex. It is well known that cerebral ischemia causes significant changes in the Na+,K+-ATPase and SOD activities. In this regard, it was documented that preservation of Na+,K+-ATPase and reinforcement of SOD activity are the possible mechanisms of HBOT in severe brain ischemia.[66] Assessment of the apoptotic cell number revealed that HBOT attenuated secondary brain damage in an experimental transient brain injury (TBI).[67] To elucidate the timing and mechanisms of HBO protection following cerebral ischemia, Veltkamp et al.[68],[69] examined the early in vivo effects of HBO by repetitive magnetic resonance imaging and BBB permeability for sodium fluorescein 2 hours after transient focal ischemia. The results showed that HBO significantly decreased abnormal diffusion weighted imaging signal volume, lesion size on T2-weighted images, BBB permeability on T1-weighted images, and vasogenic edema assessed on T2-weighted images and histologic sections after 24 hours. Another study suggested that delayed, but multiple HBOT (2.5 ATA, 2 hours per dayfor 6 consecutive days) can improve neurological function and reduce cerebral infarction after transient focal ischemia.[70] Recent data emphasize the key role of apoptosis in the spread of lesion after TBI. In this regard, Bcl-xL, Bcl-2 and Bax proteins immunostaining in the brain tissue showed a significant increase in Bcl-2 and Bcl-xL anti-apoptotic proteins after HBOT, while staining for pro-apoptotic protein Bax did not significant.[71] A study was conducted to assess HBOT effects on intracranial pressure dynamics and survival in rat severe fluid percussion brain injury, concluding HBOT during the early phase of injury significantly diminished intracranial pressure elevation rate and reduced mortality rate.[72] In regard to BBB integrity preservation with HBOT after cerebral ischemia, Veltkamp et al.[73] documented that HBO decreases ischemic degradation of cerebral microvascular laminin-5 and blocks upregulation of postischemic plasma MMP. Calvert et al.[74] tested the hypothesis that HBO alternates the expression of HIF-1α in neonatal hypoxia-ischemia. The results showed that HBOT increased glucose transporter-1, glucose transporter-3, aldolase, and lactate dehydrogenase expression, while decreased p53 expression and HIF-1α-p53 interaction. Therefore, HIF-1α phenotype alternation is one of the underlying mechanisms of HBO neuroprotection following neonatal hypoxic-ischemic injury. Effectiveness of HBO is controversial in permanent ischemia models, so that in extensive focal ischemia HBOT is only effect in early recanalization.[75] HBOT can reduce neuronal apoptosis after TBI by reducing cytochrome c secretion and Bax dimers and over-regulation of Bcl-2 expression.[76] The effects of HBOT on inflammatory infiltration and expression of MMPs in rat dynamic cortical deformation have been evaluated.[77] HBOT showed that a significant reduction in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, neutrophilic inflammatory infiltration, and MMP-9 expression. The potential neuroprotective effects of HBOT in a focal cerebral ischemia model proved with significant neuroprotection (reduction of infarct volume) at 5 hours after ischemia that lasted for 168 hours.[78] A study revealed that early intra-ischemic HBOT could reduce hemorrhagic transformation (hemoglobin content) in a rat model of focal transient cerebral ischemia.[79] A 40-day series of 80 low-pressure HBOTs following TBI increases vascular density in the damaged hippocampus and improves cognitive function.[80] Zhou et al.[81] tested the effects of HBOT on mitochondrial function, as measured by cognitive improvement and cellular adenosine triphosphate after lateral fluid-percussion injury in rat. The results showed that HBO-treated animals had significantly higher levels of cerebral ATP and cognitive recovery and lower neuronal loss in the CA2/3 and hilar regions. In another study, cerebral partial pressure of oxygen was measured using electron paramagnetic resonance oximetry before and after occlusion of the middle cerebral artery and HBO exposure in rats.[82] The results of the study revealed that measurements of the partial pressure of oxygen showed no increase in ischemic or normal hemispheres minutes after HBO exposure, despite decreasing the infarct size. Another study suggested that hyperoxia protection is due to a negative regulation of the proapoptotic function of mitochondrial translocator protein such as mitochondrial membrane potential conservation after cerebral contusion.[83] Study on optimal dosing and timing of HBOT in a rat model of transient ischemia/reperfusion revealed that oxygen is a highly neuroprotective molecule when used early and in high doses.[84] Results of a study suggested that single HBOT has a time limitation of 12 hours after TBI; meanwhile multiple HBOTs have the ability to extend the delivery time window after TBI.[85] Sun et al.[86] found that HBO decreases infarct size and reduces post-thrombolytic intracerebral hemorrhage after thromboembolic occlusion of the middle cerebral artery in rats. Also, it was documented that hyperbaric oxygenation has neuroprotective effects in middle cerebral artery occlusion-induced brain injury through reducing hydroxyl free radical formation and glutamate release.[12] Zhao et al.[87] documented that HBOT increases claudin-5 and claudin-1 expression, and decreases permeability of the BBB via the suppression of MMP-2 and MMP-9 after cerebral ischemia–reperfusion in rats, respectively. HBOT stimulates IL-10 overproduction, neurogenesis, and angiogenesis, while reduces gliosis following TBI in rat.[13] Also, HBOT reduced TBI-induced TNF-α expression and microglial activation during the acute phase of TBI resulting in a neuroprotective effect.[88] Data of another study showed that HBOT through promoting axonal sprouting and synapse remodeling can intensify neuroplastic responses, which contributes to the improvement of locomotor function following cortical ablation in rat.[89] Study on the effects of hyperbaric oxygenation on oxidative stress in acute transient focal cerebral ischemia in rats revealed significant reduction in infarct volume, activation of astrocyte, and increasing glutathione level.[90] Neonatal hypoxia-ischemia encephalopathy causes brain damage and neurodegeneration leading to cognitive and behavioral impairment. Liu et al.[91] suggested that HBOT is effective in promotion of histological and long-term functional recovery after neonatal hypoxia-ischemia brain damage due to caspase-3 inhibition and apoptosis inducing factor-mediated pathways. In regard to the effects of delayed HBOT on cerebral ischemia and its potential mechanisms, it was documented that delayed HBOT promotes neurogenesis and improves neurofunctional recovery in the late-chronic phase of stroke probably due to reactive oxygen species/HIF-1α/β-catenin pathway.[92] Despite the mentioned beneficial effects of HBOT in experimental models of stroke, Lu et al.[93] documented that HBOT increases brain damage area by activation of extracellular signal-regulated kinase (ERK) 1/2, which interrupts autophagy flux in a transient cerebral ischemic rat model. IL-10 plays an important role in the neuroprotection of HBOT against TBI, so that IL-10 deficiency aggravates the brain damage and abrogates the beneficial effects of HBOT on apoptosis, inflammation, and edema after injury.[94] A study was conducted to investigate the effect of the different hyperbaric oxygenation manipulations based on morphological, molecular-biological, and behavioral tests at 4 hours, 15 days and 75 days after TBI in rats.[95] The results showed that hyperbaric oxygenation inhibits cell apoptosis in the rat hippocampus and improves their physiological functions in the HBO-early group better than the HBO-delayed group. Another study demonstrated that HBO could enhance neuroprotection and improve prognosis through inhibiting cerebral edema, intensifying the metabolism of local neurons, reducing apoptosis, inhibiting the inflammatory reaction, and protecting BBB integrity in a blast-induced TBI model in rabbits.[96] Kraitsy et al.[97] showed that the long-term protective effects of HBOT are provided by the cortex remyelination, which is demonstrated by the recovery of sensorimotor function. Also, using diffusion-weighted imaging and DCE-magnetic resonance imaging revealed that HBO improves cytotoxic edema and impaired BBB and promotes the recovery of neurofunction after experimental TBI.[98] HBOT during the acute phase of TBI can attenuate TNF-α and transforming growth-interacting factor, and increase transforming growth factor β-1 which leads to decreased apoptosis in the affected cortex.[14] Liu et al.[99] found that daily HBOT significantly improved Morris water maze performance and attenuated edema in the ipsilateral hippocampus after TBI, suggesting that the therapeutic effect of HBO is at least partially mediated through reducing brain edema. The effects of HBO on cognitive dysfunction showed that HBOT, provided 5–7 days after craniocerebral trauma, improves cognitive function and neuroplasticity in a controlled cortical impact rat model.[100] Study of the relative neuroprotective effects HBOT and TLR4 knockout following temporary middle cerebral artery occlusion in mouse revealed that a single HBOT immediately after occlusion and after 24 hours reperfusion significantly reduces edema and improves perfusion, while, TLR4 knockout protects mice against ischemia but to a lesser extent than HBOT.[101] It was documented that HBOT due to inhibition of the TLR4/NF-κB signaling pathway protects the neurons after traumatic injury in rat, so that significantly inhibits the activation of the TLR4/NF-κB signaling pathway, reduces TNF-α, caspase-3, IL-1β and IL-6 expression, and reduces neural apoptosis and improves the neurological function.[102] HBOT increased expression of the heme oxygenase, nuclear factor erythroid 2-related factor 2 (Nrf2), and quinine oxidoreductase 1 in the brain tissue around the lesion and also improved neurological function after TBI.[103] A study revealed that HBO reduces IL-1β and IL-18 and suppresses protein expression of inflammasome components, along with high-mobility group box 1 reduction after TBI in the brain and serum.[104] In regard to repetitive mild TBI, it was found that HBOT significantly decreased the magnetic resonance imaging-identified abnormalities and tissue histopathology.[105] HBOT ameliorates TBI-induced depression-like behavior by reducing neuroinflammation if early intervention is possible, suggesting a possible mechanism by which depression-like behavior recovery might occur.[106] Results of a study showed that immediate and delayed HBOT for moderate TBI in mice have similar effects, so that displayed significant improvement in learning abilities, decreased neuronal loss and reactive astrocytes, and increased myelin basic protein.[107] Recently, it was found that HBO promotes neural stem cell proliferation and migration to the lesion area by activating VEGF/ERK signaling on day 7 after TBI.[108] It is well known that the nucleotide binding oligomerization domain like receptor family pyrin domain containing 3 (NLRP 3) inflammasome has been implicated in the secondary injury of TBI. In this regard, Qian et al.[109] documented that HBO improves motor score and reduces brain edema following TBI, along with IL 1β, IL 18, and NLRP 3 inflammasome components reduction. The results revealed that HBO decreases inflammation via modulation of microglial NLRP-3-inflammasome signaling. HBOT following hyperglycemic middle cerebral artery occlusion in rat reduces hemorrhagic transformation and infarction volume via ATP/NAD+/Sirt1 pathway which may be a promising approach for diabetic patients with acute ischemic stroke.[110] Multiple HBOT significantly decrease the expression of c-jun, c-fos, and Bax, while increase the expression of Bcl-2, neurotrophin-3, glial cell line-derived neurotrophic factor, BDNF, and nerve growth factor.[111] Also, HBO exposure through increasing tight junction protein zonula occludens-1 and caveolin-1 improved BBB permeability following global cerebral ischemia/reperfusion injury in rat.[112] He et al.[113] found that HBOT attenuates neuronal apoptosis via Akt/GSK3β/β-catenin pathway after TBI.

Nerve injury

Muscle paralysis and neuropathic pain due to the destruction of motor and sensory neurons are among the most common symptoms of nerve injuries.[114],[115] Meanwhile, neuroinflammation, oxidative stress, excitotoxicity, apoptosis, and neurotrophic support deficit are some of the mechanisms involved in neural degeneration after nerve injury.[116],[117],[118] In this regard, using the rat sciatic nerve model, the effect of HBO on peripheral nerve healing after destruction was evaluated.[119] Results of this study suggested that HBOT for 1 week following microsurgical repair promotes functional recovery in transected peripheral nerves. Also, another study concluded that HBO effectively saves fibers from ischemia.[120] Although, regard to rat peroneal nerve crush and transection injury there were no HBO-related changes in nerve/muscle force measurements and edema.[121],[122] Whereas, a study on the regenerative effects of HBO on crushed sciatic nerve injury suggested that therapies consisting of 100% oxygen under pressure can improve the healing of peripheral nerve in rabbits.[123] HBOT (first at 0, 4, and 8 hours postoperatively and then every 8 hours) stimulates axonal outgrowth following a sciatic nerve crush lesion in rat, evaluated using the pinch-reflex test and with neurofilament staining.[124] Whereas, another study concluded that HBOT (twice daily for 3 consecutive days), had no influence on functional recovery after standard nerve crush injuries on sciatic nerves of rats using walking-track analysis.[125] After that, some investigators studied the effect of HBOT on axonal outgrowth in cellular and acellular nerve grafts of sciatic nerves in rat. The axonal outgrowth was significantly longer in animals treated with HBO after cellular nerve grafting,[126] in contrast to acellular nerve grafts with no beneficial effects on axonal outgrowth.[127] Another study confirmed that HBOT could not restore the gait or the strength of muscle after 90 days with nerve transection and repair or with nerve crush injury in rats.[128] Mrsić-Pelcić et al.[129] found that HBOT prevented ischemia-induced changes in the Na+,K+-ATPase activity after HBO administration in the optic nerves of global cerebral ischemia-exposed rats, while the level of the SOD activity in the ischemic animals was not changed. Evaluation of long-lasting effects of hyperbaric oxygenation on transected sciatic nerve and repaired with microsurgery showed functional recovery after 7 weeks.[130] Evaluation of the effects of HBOT on the histological pattern of damaged facial nerve in rabbits indicated an increase in the mean axon diameter 2 weeks after injury.[131] In spite of protective effects of HBOT in peripheral nerve injury, some evidence revealed that the ERK1/2 and p38 have been differently activated in the dorsal root ganglion by prolonged HBO exposure.[132] A study showed that HBOT reduces neuropathic pain and inhibits intra-neuronal TNF-α production after chronic constrictive injury.[133] Analysis of the thermal hyperalgesia, mechanical allodynia, and neurochemical changes of neuropathic pain in rat sciatic nerve injury showed that repetitive HBOT greatly inhibited behavioral signs of neuropathic pain and nerve injury-induced induction of c-Fos and activation of astrocytes, and increased phosphorylation of N-methyl D-aspartate receptor subtype 2B receptor and the subsequent Ca2+-dependent signals in rats.[134] Pre- and post-HBOT inhibits neuropathic pain following chronic constriction injury in rats through the regulation of neuronal and inducible NOS expression in the spinal cord, demonstrating that HBO has therapeutic effects on neuropathic pain.[8] The role of brain opioid receptors in the anti-allodynic properties of HBO following crush-induced neuropathic pain in rats was investigated in another study.[135] Data analysis of this study revealed that HBOT significantly decreased the nerve crush-induced allodynia, whereas, this anti-allodynic effect by the opioid antagonist naltrexone was reversed. Another study conducted to specify the effect of different times of HBOT application on transected-sciatic nerve regeneration using standard microsurgical techniques.[136] The results showed the best gait analysis and less fibrosis with HBOT started at postoperative first hour compared to postoperative first and second week. In regard to the neuroprotective mechanism of HBOT on chronic constriction-induced neuropathic pain, it was revealed the microglial mitophagy involvement.[137] Results of our laboratory revealed that pre- and post- HBOT had neuroprotective properties following sciatic nerve degeneration through decreasing lipid peroxidation, increasing SOD and catalase activities, attenuating caspase-3 and cyclooxygenase-2 expression, and increasing S100β expression.[9] Recently, it was found that iNOS and neuronal NOS levels were significantly decreased with HBOT following chronic construction injury in rats.[138]

Neurodegenerative disease

Neurodegenerative diseases are associated with progressive nerve cell damage and neuronal loss that impair motor or cognitive function.[139] On the other hand, oxidative stress and inflammatory response play an important role in the pathogenesis of neurodegenerative diseases.[140],[141],[142] Dave et al.[143] found that HBOT in an experimental motor neuron disease significantly ameliorates mitochondrial dysfunction in the spinal cord and motor cortex, meanwhile greatly delays the disease onset. Chen et al.[144] documented that HBO prevents cognitive impairments in D-galactose induced aging model in mice due to reducing oxidative stress and blocking NF-κB pathway. Attenuation of neuroinflammatory processes is another possible mechanism underlying the effect of HBO on Alzheimer’s disease through decreasing microgliosis, astrogliosis, TNF-α, and IL-1β and increasing scavenger receptor A, arginase1, IL-4, and IL-10 expression.[145] Research on Parkinson’s disease has shown that 11-week exposure to mild HBO inhibits the decrease of dopaminergic neurons in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced Parkinson’s disease.[146]

Neurotoxic injury

For the first time, the effect of HBOT on the peripheral nerve disorder produced by administration of clioquinol, an antifungal and antiprotozoal drug which is neurotoxic in large doses, to rabbits was studied.[147] The damage of myelin and axons, which was apparent after administration of clioquinol, decreased in grade with HBO. In another study, the effect of HBO on streptozotocin-induced diabetic neuropathy was investigated.[148] The findings indicated that HBOT will partially reverse induced neuropathy in chronic diabetes. In contrast, Aydin et al.[149] did not document any beneficial effects of HBOT on nerve regeneration in early diabetes. In regard to the protective effects of HBOT following severe carbon monoxide neurotoxicity, it was found that HBO is not effective in preventing neurologic sequelae in mice following severe carbon monoxide neurotoxicity.[150]


  In Vitro Studies Top


A few numbers of in vitro studies regarding HBO neuroprotection and its basic molecular mechanisms began to accumulate (Additional Table 6). In spite of the results suggested that activation of N-methyl-D-aspartate receptors and nitric oxide production are involved in the neurotoxicity produced by prolonged HBO exposure (6 ATA for 30, 60, and 90 minutes) in primary rat cortical cultures,[151] Günther et al.[152] found that HBO had neither favorable nor unfavorable effects on the early morphological and functional restitution of ischemically damaged primary corticoencephalic cell cultures of rats under Hypoxia and glucose-deprivation (in vitro ischemia). β-Catenin, a protein involved in Wnt signaling and cell adhesion, plays an important role in the development of nervous system. In this regard, it was documented that HBOT intensifies the neural stem cell proliferation and neurogenesis by β-catenin-induced activated Neurogenin 1 gene and suppresses astrocytogenesis by β-catenin-induced down-regulated bone morphogenetic protein 4 gene.[153] An in vitro study revealed that HBO via the induction of heat shock protein 32 protected cultured spinal neurons from oxidative and oxygen glucose deprivation injury, while HBO through reactive oxygen species/p38 mitogen-activated protein kinase/Nrf2 pathway induced the expression of heat shock protein 32.[154] Another study documented that in vitro HBO after cell injury significantly accelerated neural stem cell proliferation and the VEGF/phospho-ERK pathway.[108] Examination of the effect of HBOT on the neuroprotective factor secretion, proliferation, and BDNF-release in fibroblasts and mesenchymal stem cells showed a significant increased proliferation of fibroblasts and altered the protein expression pattern in mesenchymal stem cells after 5 days of HBOT.[155] Also, it was found that HBOT promotes differentiation of neural stem cells into oligodendrocytes and neurons and reduces the number of astrocytes via regulation of Wnt3/β-catenin and BMP-2 signaling pathways.[156]


  Clinical Trials Top


Despite the growing body of preclinical evidence confirming HBOT neuroprotection, few clinical studies have been performed and therefore limited information is currently available, which are summarized in Additional Table 7. In regard to the neuroprotective effects of HBOT against spinal cord injuries, results of a clinical trial study indicated that 8 weeks of HBOT can significantly improve nerve function and consequently promote daily life activities in the patients with incomplete SCI.[157] Another randomized clinical trial studied the effect of HBO in 79 patients with acute SCI.[158] Results of this study showed that plasma HMGB1 and NF-κB expression down-regulated with HBOT in patients on days 3, 7, 10 and 30, and meanwhile F-wave chronodispersion decreased with HBOT on days 10 and 30. Also, American Spinal Injury Association and Frankel Grade motor/pain scores on day 30 were significantly improved in the treatment group.

In regard to brain injuries, results of a prospective randomized trial showed that HBOT did not increase the number of patients in the favorable outcome categories following severely brain injury.[172] A double-blind pilot study suggested that HBO improves outcome after acute ischemic stroke.[159] Rockswold et al.[160] for the first time demonstrated a prolonged effect of HBOT on cerebral blood flow and cerebral metabolism in severely brain injured patients, while, the increased cerebral metabolic rate of oxygen and decreased ventricular cerebrospinal fluid lactate levels after therapy indicated that HBO may improve aerobic metabolism in these patients. Another study documented that HBOT could improve obviously brain electric activity mapping, Glasgow coma and outcome scales in patients with severe brain injury, and decrease the morbidity and mortality.[161] A study was designed to investigate the efficacy, safety, and feasibility of HBO (60 minutes with 100% oxygen to 2.5 ATA) in 33 ischemic stroke patients.[173] Compared to medication treatment alone, HBOT was more effective in controlling epilepsy, improving clinical symptoms, and relieving hydrocephalus in patients with post-brain injury neural status.[162] Treatment of chronic brain injury with HBOT significantly improved motor skills, daily living, communication, and socialization.[163] Results of a study on the metabolism and cerebral circulation of patients in the subacute phase of head injury showed that HBOT significantly decreased both pulsatility index and jugular venous lactate after HBOT.[164] To assess the beneficial effects of HBOT on the prognosis of patients with subacute TBI , the clinical status of the patients were assessed before and 3 to 6 months after HBOT with the Glasgow outcome and Glasgow coma scales.[11] The Glasgow coma and outcome scales of the HBOT group were improved 6 months after HBOT, with minimal adverse side effects. Meanwhile, another study revealed that HBOT (2.4 ATA) following mild TBI had no effect on post-concussive symptoms.[174] Evaluation of the whether elevated dissolved oxygen by HBOT could activate neuroplasticity after stroke, revealed that HBOT significantly improves neurological outcome even in the late chronic stage.[165] A prospective, randomized phase II clinical trial revealed that combined hyperbaric hyperoxia/normobaric hyperoxia therapies after severe TBI significantly improved oxidative metabolism markers, decreased intracranial hypertension, and improved markers of cerebral toxicity, while the mortality significantly reduced.[166] Boussi-Gross et al.[167] tested the effect of HBOT on brain function and quality of life in patients with mild TBI. Results of this study revealed that HBOT induces neuroplasticity and improves quality of life with prolonged post-concussion syndrome. However, another studies demonstrated that HBO at either 1.5, 2.0 or 2.4 ATA equivalent had no effect on postconcussion symptoms after TBI.[175],[176],[177],[178] A study conducted to evaluate the safety and potential long-term neurological consequences of HBOT on intracerebral hemorrhage in diabetic patients.[168] Results of this study showed that early HBOT is safe and effective in terms of long-term neurological outcome in diabetic patients suffering from intracerebral hemorrhage. Recently, a retrospective analysis was performed on 62 consecutive patients prescribed for HBOT after stroke.[169] Results of this study showed that some patients (n = 24) significantly benefitted from HBOT by improving their clinical neurological status and quality of life.

In regard to nerve injuries, a clinical trial conducted in patients with idiopathic trigeminal neuralgia supported that one course of HBOT (10 consecutive days) is an effective approach for treating neuropathic pain in human with produced a long-lasting, rapid-onset, and dose-dependent analgesic effects.8

In regard to neurodegenerative disease, a phase I safety study and a phase II efficacy study of HBOT in patients with ALS did not recommended HBOT in ALS patients.[179],[180] Some studies conducted on hyperbaric-oxygen therapy of multiple sclerosis. Results of a randomized, placebo-controlled, double-blind study suggested a positive effect of HBO on advanced multiple sclerosis.[170] In contrast, short-term results of a placebo-controlled, double-blind trial did not support the claims made for HBO in the management of multiple sclerosis,[181] similar to some other studies.[182],[183],[184],[185],[186],[187]

In regard to neurotoxic injury, results of a study suggested that repetition of HBOT prevents the delayed neuropsychiatric sequelae of carbon monoxide poisoning when applied individually with monitoring of quantitative electroencephalography as an indicator of efficacy.[171]


  Conclusion Top


In recent years, HBOT has attracted considerable attention because of its biological properties. Neuroprotection benefits of HBOT, as a therapeutic option, confirmed with a lot of preclinical in vivo and in vitro studies. These beneficial effects have been mainly attributed to anti-oxidative, anti-inflammatory, and anti-apoptotic properties, in addition to improvement of oxygen supply and neural metabolism and stimulating autophagy. The evidence presented in this review indicates the potential of HBOT in treatment and prevention of a variety of injuries to the nervous system. Meanwhile, because limited data is available to demonstrate the neuroprotective effects of HBOT in humans, newly designed clinical trials are needed on HBOT’s neuroprotection and its possible mechanisms as well as the course and dose of HBOT.

Author contributions

FA and ARK designed and wrote the manuscript. Both authors read and approved the final manuscript.

Conflicts of interest

The authors have no conflicts of interests to declare.

Financial support

None.

Copyright license agreement

The Copyright License Agreement has been signed by both authors before publication.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Additional files:

Additional Table 1: Summary of studies regarding the effects of HBOT against spinal cord injury.

Additional Table 2: Summary of studies regarding the effects of HBOT against brain injury.

Additional Table 3: Summary of studies of the effects of HBOT against nerve injury.

Additional Table 4: Summary of studies of the effects of HBOT against neurodegenerative diseases.

Additional Table 5: Summary of studies of the effects of HBOT against neurotoxic injury.

Additional Table 6: Summary of in vitro studies on neuroprotective effects of HBOT.

Additional Table 7: Summary of clinical trials on neuroprotective effects of HBOT.



 
  References Top

1.
Thom SR. Hyperbaric oxygen: its mechanisms and efficacy. Plast Reconstr Surg. 2011;127 Suppl 1:131s-141s.  Back to cited text no. 1
    
2.
Michalski D, Härtig W, Schneider D, Hobohm C. Use of normobaric and hyperbaric oxygen in acute focal cerebral ischemia - a preclinical and clinical review. Acta Neurol Scand. 2011;123:85-97.  Back to cited text no. 2
    
3.
Huang H, Xue L, Zhang X, et al. Hyperbaric oxygen therapy provides neuroprotection following spinal cord injury in a rat model. Int J Clin Exp Pathol. 2013;6:1337-1342.  Back to cited text no. 3
    
4.
Zhou BC, Liu LJ, Liu B. Neuroprotection of hyperbaric oxygen therapy in sub-acute traumatic brain injury: not by immediately improving cerebral oxygen saturation and oxygen partial pressure. Neural Regen Res. 2016;11:1445-1449.  Back to cited text no. 4
    
5.
Chazalviel L, Haelewyn B, Degoulet M, et al. Hyperbaric oxygen increases tissue-plasminogen activator-induced thrombolysis in vitro, and reduces ischemic brain damage and edema in rats subjected to thromboembolic brain ischemia. Med Gas Res. 2016;6:64-69.  Back to cited text no. 5
    
6.
Chen X, Li Y, Chen W, Nong Z, Huang J, Chen C. Protective effect of hyperbaric oxygen on cognitive impairment induced by D-galactose in mice. Neurochem Res. 2016;41:3032-3041.  Back to cited text no. 6
    
7.
Pan X, Chen C, Huang J, Wei H, Fan Q. Neuroprotective effect of combined therapy with hyperbaric oxygen and madopar on 6-hydroxydopamine-induced Parkinson’s disease in rats. Neurosci Lett. 2015;600:220-225.  Back to cited text no. 7
    
8.
Han G, Li L, Meng LX. Effects of hyperbaric oxygen on pain-related behaviors and nitric oxide synthase in a rat model of neuropathic pain. Pain Res Manag. 2013;18:137-141.  Back to cited text no. 8
    
9.
Shams Z, Khalatbary AR, Ahmadvand H, Zare Z, Kian K. Neuroprotective effects of hyperbaric oxygen (HBO) therapy on neuronal death induced by sciatic nerve transection in rat. BMC Neurol. 2017;17:220.  Back to cited text no. 9
    
10.
Brewer AL, Shirachi DY, Quock RM, Craft RM. Effect of hyperbaric oxygen on chemotherapy-induced neuropathy in male and female rats. Behav Pharmacol. 2020;31:61-72.  Back to cited text no. 10
    
11.
Lin JW, Tsai JT, Lee LM, et al. Effect of hyperbaric oxygen on patients with traumatic brain injury. Acta Neurochir Suppl. 2008;101:145-149.  Back to cited text no. 11
    
12.
Yang ZJ, Xie Y, Bosco GM, Chen C, Camporesi EM. Hyperbaric oxygenation alleviates MCAO-induced brain injury and reduces hydroxyl radical formation and glutamate release. Eur J Appl Physiol. 2010;108:513-522.  Back to cited text no. 12
    
13.
Lin KC, Niu KC, Tsai KJ, et al. Attenuating inflammation but stimulating both angiogenesis and neurogenesis using hyperbaric oxygen in rats with traumatic brain injury. J Trauma Acute Care Surg. 2012;72:650-659.  Back to cited text no. 13
    
14.
Wee HY, Lim SW, Chio CC, Niu KC, Wang CC, Kuo JR. Hyperbaric oxygen effects on neuronal apoptosis associations in a traumatic brain injury rat model. J Surg Res. 2015;197:382-389.  Back to cited text no. 14
    
15.
Sunami K, Takeda Y, Hashimoto M, Hirakawa M. Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery. Crit Care Med. 2000;28:2831-2836.  Back to cited text no. 15
    
16.
Calvert JW, Cahill J, Zhang JH. Hyperbaric oxygen and cerebral physiology. Neurol Res. 2007;29:132-141.  Back to cited text no. 16
    
17.
Amar AP, Levy ML. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery. 1999;44:1027-1039; discussion 1039-1040.  Back to cited text no. 17
    
18.
Hall ED. Lipid antioxidants in acute central nervous system injury. Ann Emerg Med. 1993;22:1022-1027.  Back to cited text no. 18
    
19.
Popovich PG, Wei P, Stokes BT. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol. 1997;377:443-464.  Back to cited text no. 19
    
20.
Liu XZ, Xu XM, Hu R, et al. Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci. 1997;17:5395-5406.  Back to cited text no. 20
    
21.
Khalatbary AR. Natural polyphenols and spinal cord injury. Iran Biomed J. 2014;18:120-129.  Back to cited text no. 21
    
22.
Balentine JD. Central necrosis of the spinal cord induced by hyperbaric oxygen exposure. J Neurosurg. 1975;43:150-155.  Back to cited text no. 22
    
23.
Higgins AC, Pearlstein RD, Mullen JB, Nashold BS Jr. Effects of hyperbaric oxygen therapy on long-tract neuronal conduction in the acute phase of spinal cord injury. J Neurosurg. 1981;55:501-510.  Back to cited text no. 23
    
24.
Murakami N, Horinouchi T, Sakurai M, et al. Hyperbaric oxygen therapy given 30 minutes after spinal cord ischemia attenuates selective motor neuron death in rabbits. Crit Care Med. 2001;29:814-818.  Back to cited text no. 24
    
25.
Huang L, Mehta MP, Nanda A, Zhang JH. The role of multiple hyperbaric oxygenation in expanding therapeutic windows after acute spinal cord injury in rats. J Neurosurg. 2003;99:198-205.  Back to cited text no. 25
    
26.
Huang L, Mehta MP, Eichhorn JH, Nanda A, Zhang JH. Multiple hyperbaric oxygenation (HBO) expands the therapeutic window in acute spinal cord injury in rats. Acta Neurochir Suppl. 2003;86:433-438.  Back to cited text no. 26
    
27.
Kahraman S, Düz B, Kayali H, et al. Effects of methylprednisolone and hyperbaric oxygen on oxidative status after experimental spinal cord injury: a comparative study in rats. Neurochem Res. 2007;32:1547-1551.  Back to cited text no. 27
    
28.
Tai PA, Chang CK, Niu KC, Lin MT, Chiu WT, Lin CM. Attenuating experimental spinal cord injury by hyperbaric oxygen: stimulating production of vasculoendothelial and glial cell line-derived neurotrophic growth factors and interleukin-10. J Neurotrauma. 2010;27:1121-1127.  Back to cited text no. 28
    
29.
Dayan K, Keser A, Konyalioglu S, et al. The effect of hyperbaric oxygen on neuroregeneration following acute thoracic spinal cord injury. Life Sci. 2012;90:360-364.  Back to cited text no. 29
    
30.
Yang J, Wang G, Gao C, Shao G, Kang N. Effects of hyperbaric oxygen on MMP-2 and MMP-9 expression and spinal cord edema after spinal cord injury. Life Sci. 2013;93:1033-1038.  Back to cited text no. 30
    
31.
Yang J, Liu X, Zhou Y, Wang G, Gao C, Su Q. Hyperbaric oxygen alleviates experimental (spinal cord) injury by downregulating HMGB1/NF-κB expression. Spine (Phila Pa 1976). 2013;38:E1641-1648.  Back to cited text no. 31
    
32.
Zhou Y, Liu XH, Qu SD, et al. Hyperbaric oxygen intervention on expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in spinal cord injury models in rats. Chin Med J (Engl). 2013;126:3897-3903.  Back to cited text no. 32
    
33.
Tan J, Zhang F, Liang F, et al. Protective effects of hyperbaric oxygen treatment against spinal cord injury in rats via toll-like receptor 2/nuclear factor-κB signaling. Int J Clin Exp Pathol. 2014;7:1911-1919.  Back to cited text no. 33
    
34.
Yaman O, Yaman B, Aydın F, Var A, Temiz C. Hyperbaric oxygen treatment in the experimental spinal cord injury model. Spine J. 2014;14:2184-2194.  Back to cited text no. 34
    
35.
Liu X, Zhou Y, Wang Z, Yang J, Gao C, Su Q. Effect of VEGF and CX43 on the promotion of neurological recovery by hyperbaric oxygen treatment in spinal cord-injured rats. Spine J. 2014;14:119-127.  Back to cited text no. 35
    
36.
Geng CK, Cao HH, Ying X, Zhang HT, Yu HL. The effects of hyperbaric oxygen on macrophage polarization after rat spinal cord injury. Brain Res. 2015;1606:68-76.  Back to cited text no. 36
    
37.
Liang F, Li C, Gao C, et al. Effects of hyperbaric oxygen therapy on NACHT domain-leucine-rich-repeat- and pyrin domain-containing protein 3 inflammasome expression in rats following spinal cord injury. Mol Med Rep. 2015;11:4650-4656.  Back to cited text no. 37
    
38.
Hou YN, Ding WY, Shen Y, Yang DL, Wang LF, Zhang P. Effect of hyperbaric oxygen on MMP9/2 expression and motor function in rats with spinal cord injury. Int J Clin Exp Med. 2015;8:14926-14934.  Back to cited text no. 38
    
39.
Liu X, Yang J, Li Z, et al. Hyperbaric oxygen treatment protects against spinal cord injury by inhibiting endoplasmic reticulum stress in rats. Spine (Phila Pa 1976). 2015;40:E1276-1283.  Back to cited text no. 39
    
40.
Liu X, Li C, Liang F, Wang Y, Li Z, Yang J. Effects of hyperbaric oxygen on glucose-regulated protein 78 and c-Jun N-terminal kinase expression after spinal cord injury in rats. Int J Clin Exp Med. 2015;8:3309-3317.  Back to cited text no. 40
    
41.
Kang N, Hai Y, Yang J, Liang F, Gao CJ. Hyperbaric oxygen intervention reduces secondary spinal cord injury in rats via regulation of HMGB1/TLR4/NF-κB signaling pathway. Int J Clin Exp Pathol. 2015;8:1141-1153.  Back to cited text no. 41
    
42.
Zhang D, Zhu D, Wang F, et al. Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons. Neural Regen Res. 2020;15:1120-1132.  Back to cited text no. 42
    
43.
Sun Y, Liu D, Su P, Lin F, Tang Q. Changes in autophagy in rats after spinal cord injury and the effect of hyperbaric oxygen on autophagy. Neurosci Lett. 2016;618:139-145.  Back to cited text no. 43
    
44.
Wang Y, Li C, Gao C, et al. Effects of hyperbaric oxygen therapy on RAGE and MCP-1 expression in rats with spinal cord injury. Mol Med Rep. 2016;14:5619-5625.  Back to cited text no. 44
    
45.
Sun Y, Liu D, Wang Q, Su P, Tang Q. Hyperbaric oxygen treatment of spinal cord injury in rat model. BMC Neurol. 2017;17:128.  Back to cited text no. 45
    
46.
Sun W, Tan J, Li Z, et al. Evaluation of hyperbaric oxygen treatment in acute traumatic spinal cord injury in rats using diffusion tensor imaging. Aging Dis. 2018;9:391-400.  Back to cited text no. 46
    
47.
Ying X, Tu W, Li S, et al. Hyperbaric oxygen therapy reduces apoptosis and dendritic/synaptic degeneration via the BDNF/TrkB signaling pathways in SCI rats. Life Sci. 2019;229:187-199.  Back to cited text no. 47
    
48.
Meng XL, Hai Y, Zhang XN, et al. Hyperbaric oxygen improves functional recovery of rats after spinal cord injury via activating stromal cell-derived factor-1/CXC chemokine receptor 4 axis and promoting brain-derived neurothrophic factor expression. Chin Med J (Engl). 2019;132:699-706.  Back to cited text no. 48
    
49.
Zhou Y, Dong Q, Pan Z, et al. Hyperbaric oxygen improves functional recovery of the injured spinal cord by inhibiting inflammation and glial scar formation. Am J Phys Med Rehabil. 2019;98:914-920.  Back to cited text no. 49
    
50.
Liu F, Yang L, Liu J, et al. Evaluation of hyperbaric oxygen therapy for spinal cord injury in rats with different treatment course using diffusion tensor imaging. Spinal Cord. 2019;57:404-411.  Back to cited text no. 50
    
51.
Ikeda Y, Long DM. The molecular basis of brain injury and brain edema: the role of oxygen free radicals. Neurosurgery. 1990;27:1-11.  Back to cited text no. 51
    
52.
Siesjö BK. Basic mechanisms of traumatic brain damage. Ann Emerg Med. 1993;22:959-969.  Back to cited text no. 52
    
53.
Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci. 2017;38:1167-1186.  Back to cited text no. 53
    
54.
Weinstein PR, Hameroff SR, Johnson PC, Anderson GG. Effect of hyperbaric oxygen therapy or dimethyl sulfoxide on cerebral ischemia in unanesthetized gerbils. Neurosurgery. 1986;18:528-532.  Back to cited text no. 54
    
55.
Mink RB, Dutka AJ. Hyperbaric oxygen after global cerebral ischemia in rabbits does not promote brain lipid peroxidation. Crit Care Med. 1995;23:1398-1404.  Back to cited text no. 55
    
56.
Mink RB, Dutka AJ. Hyperbaric oxygen after global cerebral ischemia in rabbits reduces brain vascular permeability and blood flow. Stroke. 1995;26:2307-2312.  Back to cited text no. 56
    
57.
Roos JA, Jackson-Friedman C, Lyden P. Effects of hyperbaric oxygen on neurologic outcome for cerebral ischemia in rats. Acad Emerg Med. 1998;5:18-24.  Back to cited text no. 57
    
58.
Chang CF, Niu KC, Hoffer BJ, Wang Y, Borlongan CV. Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats. Exp Neurol. 2000;166:298-306.  Back to cited text no. 58
    
59.
Atochin DN, Fisher D, Demchenko IT, Thom SR. Neutrophil sequestration and the effect of hyperbaric oxygen in a rat model of temporary middle cerebral artery occlusion. Undersea Hyperb Med. 2000;27:185-190.  Back to cited text no. 59
    
60.
Badr AE, Yin W, Mychaskiw G, Zhang JH. Effect of hyperbaric oxygen on striatal metabolites: a microdialysis study in awake freely moving rats after MCA occlusion. Brain Res. 2001;916:85-90.  Back to cited text no. 60
    
61.
Yang JT, Chang CN, Lee TH, et al. Hyperbaric oxygen treatment decreases post-ischemic neurotrophin-3 mRNA down-regulation in the rat hippocampus. Neuroreport. 2001;12:3589-3592.  Back to cited text no. 61
    
62.
Badr AE, Yin W, Mychaskiw G, Zhang JH. Dual effect of HBO on cerebral infarction in MCAO rats. Am J Physiol Regul Integr Comp Physiol. 2001;280:R766-770.  Back to cited text no. 62
    
63.
Yin W, Badr AE, Mychaskiw G, Zhang JH. Down regulation of COX-2 is involved in hyperbaric oxygen treatment in a rat transient focal cerebral ischemia model. Brain Res. 2002;926:165-171.  Back to cited text no. 63
    
64.
Yang ZJ, Camporesi C, Yang X, et al. Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal dopamine release in a rat model of transient middle cerebral artery occlusion. Eur J Appl Physiol. 2002;87:101-107.  Back to cited text no. 64
    
65.
Yin D, Zhou C, Kusaka I, et al. Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model. J Cereb Blood Flow Metab. 2003;23:855-864.  Back to cited text no. 65
    
66.
Mrsić-Pelcić J, Pelcić G, Vitezić D, et al. Hyperbaric oxygen treatment: the influence on the hippocampal superoxide dismutase and Na+,K+-ATPase activities in global cerebral ischemia-exposed rats. Neurochem Int. 2004;44:585-594.  Back to cited text no. 66
    
67.
Palzur E, Vlodavsky E, Mulla H, Arieli R, Feinsod M, Soustiel JF. Hyperbaric oxygen therapy for reduction of secondary brain damage in head injury: an animal model of brain contusion. J Neurotrauma. 2004;21:41-48.  Back to cited text no. 67
    
68.
Veltkamp R, Siebing DA, Heiland S, et al. Hyperbaric oxygen induces rapid protection against focal cerebral ischemia. Brain Res. 2005;1037:134-138.  Back to cited text no. 68
    
69.
Veltkamp R, Siebing DA, Sun L, et al. Hyperbaric oxygen reduces blood-brain barrier damage and edema after transient focal cerebral ischemia. Stroke. 2005;36:1679-1683.  Back to cited text no. 69
    
70.
Yin D, Zhang JH. Delayed and multiple hyperbaric oxygen treatments expand therapeutic window in rat focal cerebral ischemic model. Neurocrit Care. 2005;2:206-211.  Back to cited text no. 70
    
71.
Vlodavsky E, Palzur E, Feinsod M, Soustiel JF. Evaluation of the apoptosis-related proteins of the BCL-2 family in the traumatic penumbra area of the rat model of cerebral contusion, treated by hyperbaric oxygen therapy: a quantitative immunohistochemical study. Acta Neuropathol. 2005;110:120-126.  Back to cited text no. 71
    
72.
Rogatsky GG, Kamenir Y, Mayevsky A. Effect of hyperbaric oxygenation on intracranial pressure elevation rate in rats during the early phase of severe traumatic brain injury. Brain Res. 2005;1047:131-136.  Back to cited text no. 72
    
73.
Veltkamp R, Bieber K, Wagner S, et al. Hyperbaric oxygen reduces basal lamina degradation after transient focal cerebral ischemia in rats. Brain Res. 2006;1076:231-237.  Back to cited text no. 73
    
74.
Calvert JW, Cahill J, Yamaguchi-Okada M, Zhang JH. Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1alpha and its downstream target genes. J Appl Physiol (1985). 2006;101:853-865.  Back to cited text no. 74
    
75.
Veltkamp R, Sun L, Herrmann O, et al. Oxygen therapy in permanent brain ischemia: potential and limitations. Brain Res. 2006;1107:185-191.  Back to cited text no. 75
    
76.
Liu Z, Jiao QF, You C, Che YJ, Su FZ. Effect of hyperbaric oxygen on cytochrome C, Bcl-2 and Bax expression after experimental traumatic brain injury in rats. Chin J Traumatol. 2006;9:168-174.  Back to cited text no. 76
    
77.
Vlodavsky E, Palzur E, Soustiel JF. Hyperbaric oxygen therapy reduces neuroinflammation and expression of matrix metalloproteinase-9 in the rat model of traumatic brain injury. Neuropathol Appl Neurobiol. 2006;32:40-50.  Back to cited text no. 77
    
78.
Henninger N, Küppers-Tiedt L, Sicard KM, Günther A, Schneider D, Schwab S. Neuroprotective effect of hyperbaric oxygen therapy monitored by MR-imaging after embolic stroke in rats. Exp Neurol. 2006;201:316-323.  Back to cited text no. 78
    
79.
Qin Z, Karabiyikoglu M, Hua Y, et al. Hyperbaric oxygen-induced attenuation of hemorrhagic transformation after experimental focal transient cerebral ischemia. Stroke. 2007;38:1362-1367.  Back to cited text no. 79
    
80.
Harch PG, Kriedt C, Van Meter KW, Sutherland RJ. Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury. Brain Res. 2007;1174:120-129.  Back to cited text no. 80
    
81.
Zhou Z, Daugherty WP, Sun D, et al. Protection of mitochondrial function and improvement in cognitive recovery in rats treated with hyperbaric oxygen following lateral fluid-percussion injury. J Neurosurg. 2007;106:687-694.  Back to cited text no. 81
    
82.
Hou H, Grinberg O, Williams B, et al. The effect of oxygen therapy on brain damage and cerebral pO(2) in transient focal cerebral ischemia in the rat. Physiol Meas. 2007;28:963-976.  Back to cited text no. 82
    
83.
Soustiel JF, Palzur E, Vlodavsky E, Veenman L, Gavish M. The effect of oxygenation level on cerebral post-traumatic apoptotsis is modulated by the 18-kDa translocator protein (also known as peripheral-type benzodiazepine receptor) in a rat model of cortical contusion. Neuropathol Appl Neurobiol. 2008;34:412-423.  Back to cited text no. 83
    
84.
Eschenfelder CC, Krug R, Yusofi AF, et al. Neuroprotection by oxygen in acute transient focal cerebral ischemia is dose dependent and shows superiority of hyperbaric oxygenation. Cerebrovasc Dis. 2008;25:193-201.  Back to cited text no. 84
    
85.
Wang GH, Zhang XG, Jiang ZL, et al. Neuroprotective effects of hyperbaric oxygen treatment on traumatic brain injury in the rat. J Neurotrauma. 2010;27:1733-1743.  Back to cited text no. 85
    
86.
Sun L, Zhou W, Mueller C, et al. Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia. J Cereb Blood Flow Metab. 2010;30:1651-1660.  Back to cited text no. 86
    
87.
Zhao H, Zhang Q, Xue Y, Chen X, Haun RS. Effects of hyperbaric oxygen on the expression of claudins after cerebral ischemia-reperfusion in rats. Exp Brain Res. 2011;212:109-117.  Back to cited text no. 87
    
88.
Lim SW, Wang CC, Wang YH, Chio CC, Niu KC, Kuo JR. Microglial activation induced by traumatic brain injury is suppressed by postinjury treatment with hyperbaric oxygen therapy. J Surg Res. 2013;184:1076-1084.  Back to cited text no. 88
    
89.
Brkic P, Stojiljkovic M, Jovanovic T, et al. Hyperbaric oxygenation improves locomotor ability by enhancing neuroplastic responses after cortical ablation in rats. Brain Inj. 2012;26:1273-1284.  Back to cited text no. 89
    
90.
Wang RY, Chang HC, Chen CH, Tsai YW, Yang YR. Effects of hyperbaric oxygenation on oxidative stress in acute transient focal cerebral ischemic rats. Eur J Appl Physiol. 2012;112:215-221.  Back to cited text no. 90
    
91.
Liu XH, Yan H, Xu M, et al. Hyperbaric oxygenation reduces long-term brain injury and ameliorates behavioral function by suppression of apoptosis in a rat model of neonatal hypoxia-ischemia. Neurochem Int. 2013;62:922-930.  Back to cited text no. 91
    
92.
Hu Q, Liang X, Chen D, et al. Delayed hyperbaric oxygen therapy promotes neurogenesis through reactive oxygen species/hypoxia-inducible factor-1α/β-catenin pathway in middle cerebral artery occlusion rats. Stroke. 2014;45:1807-1814.  Back to cited text no. 92
    
93.
Lu Y, Kang J, Bai Y, et al. Hyperbaric oxygen enlarges the area of brain damage in MCAO rats by blocking autophagy via ERK1/2 activation. Eur J Pharmacol. 2014;728:93-99.  Back to cited text no. 93
    
94.
Chen X, Duan XS, Xu LJ, et al. Interleukin-10 mediates the neuroprotection of hyperbaric oxygen therapy against traumatic brain injury in mice. Neuroscience. 2014;266:235-243.  Back to cited text no. 94
    
95.
Yang Y, Zhang YG, Lin GA, et al. The effects of different hyperbaric oxygen manipulations in rats after traumatic brain injury. Neurosci Lett. 2014;563:38-43.  Back to cited text no. 95
    
96.
Zhang Y, Yang Y, Tang H, et al. Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits. Neurochem Res. 2014;39:950-960.  Back to cited text no. 96
    
97.
Kraitsy K, Uecal M, Grossauer S, et al. Repetitive long-term hyperbaric oxygen treatment (HBOT) administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function. PLoS One. 2014;9:e97750.  Back to cited text no. 97
    
98.
Wei XE, Li YH, Zhao H, Li MH, Fu M, Li WB. Quantitative evaluation of hyperbaric oxygen efficacy in experimental traumatic brain injury: an MRI study. Neurol Sci. 2014;35:295-302.  Back to cited text no. 98
    
99.
Liu S, Liu Y, Deng S, Guo A, Wang X, Shen G. Beneficial effects of hyperbaric oxygen on edema in rat hippocampus following traumatic brain injury. Exp Brain Res. 2015;233:3359-3365.  Back to cited text no. 99
    
100.
Zhang X, Wang X, Sun X, Sun X, Zhang Y, Zhang H. Differences in cognitive function of rats with traumatic brain injuries following hyperbaric oxygen therapy. Med Sci Monit. 2016;22:2608-2615.  Back to cited text no. 100
    
101.
Pushkov D, Nicholson JD, Michowiz S, et al. Relative neuroprotective effects hyperbaric oxygen treatment and TLR4 knockout in a mouse model of temporary middle cerebral artery occlusion. Int J Neurosci. 2016;126:174-181.  Back to cited text no. 101
    
102.
Meng XE, Zhang Y, Li N, et al. Hyperbaric oxygen alleviates secondary brain injury after trauma through inhibition of TLR4/NF-κB signaling pathway. Med Sci Monit. 2016;22:284-288.  Back to cited text no. 102
    
103.
Meng XE, Zhang Y, Li N, et al. Effects of hyperbaric oxygen on the Nrf2 signaling pathway in secondary injury following traumatic brain injury. Genet Mol Res. 2016;15:gmr6933.  Back to cited text no. 103
    
104.
Geng F, Ma Y, Xing T, Zhuang X, Zhu J, Yao L. Effects of hyperbaric oxygen therapy on inflammasome signaling after traumatic brain injury. Neuroimmunomodulation. 2016;23:122-129.  Back to cited text no. 104
    
105.
Huang L, Obenaus A, Hamer M, Zhang JH. Neuroprotective effect of hyperbaric oxygen therapy in a juvenile rat model of repetitive mild traumatic brain injury. Med Gas Res. 2016;6:187-193.  Back to cited text no. 105
    
106.
Lim SW, Sung KC, Shiue YL, Wang CC, Chio CC, Kuo JR. Hyperbaric oxygen effects on depression-like behavior and neuroinflammation in traumatic brain injury rats. World Neurosurg. 2017;100:128-137.  Back to cited text no. 106
    
107.
Baratz-Goldstein R, Toussia-Cohen S, Elpaz A, Rubovitch V, Pick CG. Immediate and delayed hyperbaric oxygen therapy as a neuroprotective treatment for traumatic brain injury in mice. Mol Cell Neurosci. 2017;83:74-82.  Back to cited text no. 107
    
108.
Yang Y, Wei H, Zhou X, Zhang F, Wang C. Hyperbaric oxygen promotes neural stem cell proliferation by activating vascular endothelial growth factor/extracellular signal-regulated kinase signaling after traumatic brain injury. Neuroreport. 2017;28:1232-1238.  Back to cited text no. 108
    
109.
Qian H, Li Q, Shi W. Hyperbaric oxygen alleviates the activation of NLRP 3 inflammasomes in traumatic brain injury. Mol Med Rep. 2017;16:3922-3928.  Back to cited text no. 109
    
110.
Hu Q, Manaenko A, Bian H, et al. Hyperbaric oxygen reduces infarction volume and hemorrhagic transformation through ATP/NAD(+)/Sirt1 pathway in hyperglycemic middle cerebral artery occlusion rats. Stroke. 2017;48:1655-1664.  Back to cited text no. 110
    
111.
Xing P, Ma K, Li L, Wang D, Hu G, Long W. The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury. Acta Cir Bras. 2018;33:341-353.  Back to cited text no. 111
    
112.
Li HZ, Chen JF, Liu M, Shen J. Effect of hyperbaric oxygen on the permeability of the blood-brain barrier in rats with global cerebral ischemia/reperfusion injury. Biomed Pharmacother. 2018;108:1725-1730.  Back to cited text no. 112
    
113.
He H, Li X, He Y. Hyperbaric oxygen therapy attenuates neuronal apoptosis induced by traumatic brain injury via Akt/GSK3β/β-catenin pathway. Neuropsychiatr Dis Treat. 2019;15:369-374.  Back to cited text no. 113
    
114.
Laferrière A, Millecamps M, Xanthos DN, et al. Cutaneous tactile allodynia associated with microvascular dysfunction in muscle. Mol Pain. 2008;4:49.  Back to cited text no. 114
    
115.
Lundborg G, Rosén B. Hand function after nerve repair. Acta Physiol (Oxf). 2007;189:207-217.  Back to cited text no. 115
    
116.
Choi DW. Excitotoxic cell death. J Neurobiol. 1992;23:1261-1276.  Back to cited text no. 116
    
117.
Liu Z, Martin LJ. Motor neurons rapidly accumulate DNA single-strand breaks after in vitro exposure to nitric oxide and peroxynitrite and in vivo axotomy. J Comp Neurol. 2001;432:35-60.  Back to cited text no. 117
    
118.
Li HY, Ruan YW, Ren CR, Cui Q, So KF. Mechanisms of secondary degeneration after partial optic nerve transection. Neural Regen Res. 2014;9:565-574.  Back to cited text no. 118
    
119.
Zamboni WA, Brown RE, Roth AC, Mathur A, Stephenson LL. Functional evaluation of peripheral-nerve repair and the effect of hyperbaric oxygen. J Reconstr Microsurg. 1995;11:27-29; discussion 29-30.  Back to cited text no. 119
    
120.
Kihara M, McManis PG, Schmelzer JD, Kihara Y, Low PA. Experimental ischemic neuropathy: salvage with hyperbaric oxygenation. Ann Neurol. 1995;37:89-94.  Back to cited text no. 120
    
121.
Santos PM, Williams SL, Covey J. Peroneal motor nerve crush injury and hyperbaric oxygen effect. Laryngoscope. 1995;105:1061-1065.  Back to cited text no. 121
    
122.
Santos PM, Zamboni WA, Williams SL, Covey JF, Kienstra MA. Hyperbaric oxygen treatment after rat peroneal nerve transection and entubulation. Otolaryngol Head Neck Surg. 1996;114:424-434.  Back to cited text no. 122
    
123.
Bradshaw PO, Nelson AG, Fanton JW, Yates T, Kagan-Hallet KS. Effect of hyperbaric oxygenation on peripheral nerve regeneration in adult male rabbits. Undersea Hyperb Med. 1996;23:107-113.  Back to cited text no. 123
    
124.
Haapaniemi T, Nylander G, Kanje M, Dahlin L. Hyperbaric oxygen treatment enhances regeneration of the rat sciatic nerve. Exp Neurol. 1998;149:433-438.  Back to cited text no. 124
    
125.
Tuma Júnior P, Dias MD, Arrunátegui G, et al. Effect of hyperbaric oxygen on the regeneration of experimental crush injuries of nerves. Rev Hosp Clin Fac Med Sao Paulo. 1999;54:81-84.  Back to cited text no. 125
    
126.
Haapaniemi T, Nishiura Y, Dahlin LB. Effects of hyperbaric oxygen treatment on axonal outgrowth in sciatic nerve grafts in rats. Scand J Plast Reconstr Surg Hand Surg. 2001;35:7-11.  Back to cited text no. 126
    
127.
Nishiura Y, Haapaniemi T, Dahlin LB. Hyperbaric oxygen treatment has different effects on nerve regeneration in acellular nerve and muscle grafts. J Peripher Nerv Syst. 2001;6:73-78.  Back to cited text no. 127
    
128.
Haapaniemi T, Nishiura Y, Dahlin LB. Functional evaluation after rat sciatic nerve injury followed by hyperbaric oxygen treatment. J Peripher Nerv Syst. 2002;7:149-154.  Back to cited text no. 128
    
129.
Mrsić-Pelcić J, Pelcić G, Peternel S, Pilipović K, Simonić A, Zupan G. Effects of the hyperbaric oxygen treatment on the Na+,K+ -ATPase and superoxide dismutase activities in the optic nerves of global cerebral ischemia-exposed rats. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:667-676.  Back to cited text no. 129
    
130.
Eguiluz-Ordoñez R, Sánchez CE, Venegas A, Figueroa-Granados V, Hernández-Pando R. Effects of hyperbaric oxygen on peripheral nerves. Plast Reconstr Surg. 2006;118:350-357; discussion 358-359.  Back to cited text no. 130
    
131.
Vilela DS, Lazarini PR, Da Silva CF. Effects of hyperbaric oxygen therapy on facial nerve regeneration. Acta Otolaryngol. 2008;128:1048-1052.  Back to cited text no. 131
    
132.
Li KC, Bao XC, Fang YQ, et al. Different activation of ERK1/2 and p38 with hyperbaric oxygen in dorsal root ganglion. Undersea Hyperb Med. 2011;38:149-153.  Back to cited text no. 132
    
133.
Li F, Fang L, Huang S, et al. Hyperbaric oxygenation therapy alleviates chronic constrictive injury-induced neuropathic pain and reduces tumor necrosis factor-alpha production. Anesth Analg. 2011;113:626-633.  Back to cited text no. 133
    
134.
Gu N, Niu JY, Liu WT, et al. Hyperbaric oxygen therapy attenuates neuropathic hyperalgesia in rats and idiopathic trigeminal neuralgia in patients. Eur J Pain. 2012;16:1094-1105.  Back to cited text no. 134
    
135.
Gibbons CR, Liu S, Zhang Y, et al. Involvement of brain opioid receptors in the anti-allodynic effect of hyperbaric oxygen in rats with sciatic nerve crush-induced neuropathic pain. Brain Res. 2013;1537:111-116.  Back to cited text no. 135
    
136.
Ince B, Arslan A, Dadaci M, Oltulu P, Bilgen F. The effect of different application timings of hyperbaric oxygen treatment on nerve regeneration in rats. Microsurgery. 2016;36:586-592.  Back to cited text no. 136
    
137.
Han G, Liu K, Li L, Li X, Zhao P. The effects of hyperbaric oxygen therapy on neuropathic pain via mitophagy in microglia. Mol Pain. 2017;13:1744806917710862.  Back to cited text no. 137
    
138.
Ding Y, Yao P, Hong T, et al. Early hyperbaric oxygen effects on neuropathic pain and nitric oxide synthase isoforms in CCI rats. Oncotarget. 2018;9:7513-7521.  Back to cited text no. 138
    
139.
Choonara YE, Pillay V, du Toit LC, et al. Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders. Int J Mol Sci. 2009;10:2510-2557.  Back to cited text no. 139
    
140.
Liu Z, Zhou T, Ziegler AC, Dimitrion P, Zuo L. Oxidative stress in neurodegenerative diseases: from molecular mechanisms to clinical applications. Oxid Med Cell Longev. 2017;2017:2525967.  Back to cited text no. 140
    
141.
Albers DS, Beal MF. Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease. J Neural Transm Suppl. 2000;59:133-154.  Back to cited text no. 141
    
142.
Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease--a double-edged sword. Neuron. 2002;35:419-432.  Back to cited text no. 142
    
143.
Dave KR, Prado R, Busto R, et al. Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron disease in Wobbler mice. Neuroscience. 2003;120:113-120.  Back to cited text no. 143
    
144.
Chen C, Huang L, Nong Z, et al. Hyperbaric oxygen prevents cognitive impairments in mice induced by d-galactose by improving cholinergic and anti-apoptotic functions. Neurochem Res. 2017;42:1240-1253.  Back to cited text no. 144
    
145.
Shapira R, Solomon B, Efrati S, Frenkel D, Ashery U. Hyperbaric oxygen therapy ameliorates pathophysiology of 3xTg-AD mouse model by attenuating neuroinflammation. Neurobiol Aging. 2018;62:105-119.  Back to cited text no. 145
    
146.
Kusuda Y, Takemura A, Nakano M, Ishihara A. Mild hyperbaric oxygen inhibits the decrease of dopaminergic neurons in the substantia nigra of mice with MPTP-induced Parkinson’s disease. Neurosci Res. 2018;132:58-62.  Back to cited text no. 146
    
147.
Mukoyama M, Iida M, Sobue I. Hyperbaric oxygen therapy for peripheral nerve damage induced in rabbits with clioquinol. Exp Neurol. 1975;47:371-380.  Back to cited text no. 147
    
148.
Low PA, Schmelzer JD, Ward KK, Curran GL, Poduslo JF. Effect of hyperbaric oxygenation on normal and chronic streptozotocin diabetic peripheral nerves. Exp Neurol. 1988;99:201-212.  Back to cited text no. 148
    
149.
Aydin A, Ozden BC, Karamürsel S, Solakoğlu S, Aktaş S, Erer M. Effect of hyperbaric oxygen therapy on nerve regeneration in early diabetes. Microsurgery. 2004;24:255-261.  Back to cited text no. 149
    
150.
Gilmer B, Kilkenny J, Tomaszewski C, Watts JA. Hyperbaric oxygen does not prevent neurologic sequelae after carbon monoxide poisoning. Acad Emerg Med. 2002;9:1-8.  Back to cited text no. 150
    
151.
Huang KL, Wu JN, Lin HC, Mao SP, Kang B, Wan FJ. Prolonged exposure to hyperbaric oxygen induces neuronal damage in primary rat cortical cultures. Neurosci Lett. 2000;293:159-162.  Back to cited text no. 151
    
152.
Günther A, Manaenko A, Franke H, et al. Early biochemical and histological changes during hyperbaric or normobaric reoxygenation after in vitro ischaemia in primary corticoencephalic cell cultures of rats. Brain Res. 2002;946:130-138.  Back to cited text no. 152
    
153.
Zhang XY, Yang YJ, Xu PR, et al. The role of β-catenin signaling pathway on proliferation of rats neural stem cells after hyperbaric oxygen therapy in vitro. Cell Mol Neurobiol. 2011;31:101-109.  Back to cited text no. 153
    
154.
Huang G, Diao J, Yi H, Xu L, Xu J, Xu W. Signaling pathways involved in HSP32 induction by hyperbaric oxygen in rat spinal neurons. Redox Biol. 2016;10:108-118.  Back to cited text no. 154
    
155.
Schulze J, Kaiser O, Paasche G, et al. Effect of hyperbaric oxygen on BDNF-release and neuroprotection: Investigations with human mesenchymal stem cells and genetically modified NIH3T3 fibroblasts as putative cell therapeutics. PLoS One. 2017;12:e0178182.  Back to cited text no. 155
    
156.
Chen C, Yang Y, Yao Y. HBO Promotes the differentiation of neural stem cells via interactions between the Wnt3/β-Catenin and BMP2 signaling pathways. Cell Transplant. 2019;28:1686-1699.  Back to cited text no. 156
    
157.
Feng JJ, Li YH. Effects of hyperbaric oxygen therapy on depression and anxiety in the patients with incomplete spinal cord injury (a STROBE-compliant article). Medicine (Baltimore). 2017;96:e7334.  Back to cited text no. 157
    
158.
Sun L, Zhao L, Li P, et al. Effect of hyperbaric oxygen therapy on HMGB1/NF-κB expression and prognosis of acute spinal cord injury: A randomized clinical trial. Neurosci Lett. 2019;692:47-52.  Back to cited text no. 158
    
159.
Nighoghossian N, Trouillas P, Adeleine P, Salord F. Hyperbaric oxygen in the treatment of acute ischemic stroke. A double-blind pilot study. Stroke. 1995;26:1369-1372.  Back to cited text no. 159
    
160.
Rockswold SB, Rockswold GL, Vargo JM, et al. Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients. J Neurosurg. 2001;94:403-411.  Back to cited text no. 160
    
161.
Ren H, Wang W, Ge Z. Glasgow Coma Scale, brain electric activity mapping and Glasgow Outcome Scale after hyperbaric oxygen treatment of severe brain injury. Chin J Traumatol. 2001;4:239-241.  Back to cited text no. 161
    
162.
Shi XY, Tang ZQ, Xiong B, et al. Cerebral perfusion SPECT imaging for assessment of the effect of hyperbaric oxygen therapy on patients with postbrain injury neural status. Chin J Traumatol. 2003;6:346-349.  Back to cited text no. 162
    
163.
Golden Z, Golden CJ, Neubauer RA. Improving neuropsychological function after chronic brain injury with hyperbaric oxygen. Disabil Rehabil. 2006;28:1379-1386.  Back to cited text no. 163
    
164.
Nakamura T, Kuroda Y, Yamashita S, et al. Hyperbaric oxygen therapy for consciousness disturbance following head injury in subacute phase. Acta Neurochir Suppl. 2008;102:21-24.  Back to cited text no. 164
    
165.
Efrati S, Fishlev G, Bechor Y, et al. Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial. PLoS One. 2013;8:e53716.  Back to cited text no. 165
    
166.
Rockswold SB, Rockswold GL, Zaun DA, Liu J. A prospective, randomized phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg. 2013;118:1317-1328.  Back to cited text no. 166
    
167.
Boussi-Gross R, Golan H, Fishlev G, et al. Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial. PLoS One. 2013;8:e79995.  Back to cited text no. 167
    
168.
Xu Q, Fan SB, Wan YL, Liu XL, Wang L. The potential long-term neurological improvement of early hyperbaric oxygen therapy on hemorrhagic stroke in the diabetics. Diabetes Res Clin Pract. 2018;138:75-80.  Back to cited text no. 168
    
169.
Golan H, Makogon B, Volkov O, Smolyakov Y, Hadanny A, Efrati S. Imaging-based predictors for hyperbaric oxygen therapy outcome in post-stroke patients. Report 1. Med Hypotheses. 2020;136:109510.  Back to cited text no. 169
    
170.
Fischer BH, Marks M, Reich T. Hyperbaric-oxygen treatment of multiple sclerosis. A randomized, placebo-controlled, double-blind study. N Engl J Med. 1983;308:181-186.  Back to cited text no. 170
    
171.
Murata M, Suzuki M, Hasegawa Y, Nohara S, Kurachi M. Improvement of occipital alpha activity by repetitive hyperbaric oxygen therapy in patients with carbon monoxide poisoning: a possible indicator for treatment efficacy. J Neurol Sci. 2005;235:69-74.  Back to cited text no. 171
    
172.
Rockswold GL, Ford SE, Anderson DC, Bergman TA, Sherman RE. Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. J Neurosurg. 1992;76:929-934.  Back to cited text no. 172
    
173.
Rusyniak DE, Kirk MA, May JD, et al. Hyperbaric oxygen therapy in acute ischemic stroke: results of the hyperbaric oxygen in acute ischemic stroke trial pilot study. Stroke. 2003;34:571-574.  Back to cited text no. 173
    
174.
Wolf G, Cifu D, Baugh L, Carne W, Profenna L. The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury. J Neurotrauma. 2012;29:2606-2612.  Back to cited text no. 174
    
175.
Cifu DX, Hart BB, West SL, Walker W, Carne W. The effect of hyperbaric oxygen on persistent postconcussion symptoms. J Head Trauma Rehabil. 2014;29:11-20.  Back to cited text no. 175
    
176.
Cifu DX, Walker WC, West SL, et al. Hyperbaric oxygen for blast-related postconcussion syndrome: three-month outcomes. Ann Neurol. 2014;75:277-286.  Back to cited text no. 176
    
177.
Walker WC, Franke LM, Cifu DX, Hart BB. Randomized, sham-controlled, feasibility trial of hyperbaric oxygen for service members with postconcussion syndrome: cognitive and psychomotor outcomes 1 week postintervention. Neurorehabil Neural Repair. 2014;28:420-432.  Back to cited text no. 177
    
178.
Miller RS, Weaver LK, Bahraini N, et al. Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent postconcussion symptoms: a randomized clinical trial. JAMA Intern Med. 2015;175:43-52.  Back to cited text no. 178
    
179.
Steele J, Matos LA, Lopez EA, et al. A Phase I safety study of hyperbaric oxygen therapy for amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004;5:250-254.  Back to cited text no. 179
    
180.
Steele J, Zutshi D, Bradley WG. Negative results of a phase II study of hyperbaric oxygen therapy for amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2007;8:274-275.  Back to cited text no. 180
    
181.
Barnes MP, Bates D, Cartlidge NE, French JM, Shaw DA. Hyperbaric oxygen and multiple sclerosis: short-term results of a placebo-controlled, double-blind trial. Lancet. 1985;1:297-300.  Back to cited text no. 181
    
182.
Neiman J, Nilsson BY, Barr PO, Perrins DJ. Hyperbaric oxygen in chronic progressive multiple sclerosis: visual evoked potentials and clinical effects. J Neurol Neurosurg Psychiatry. 1985;48:497-500.  Back to cited text no. 182
    
183.
Wood J, Stell R, Unsworth I, Lance JW, Skuse N. A double-blind trial of hyperbaric oxygen in the treatment of multiple sclerosis. Med J Aust. 1985;143:238-240.  Back to cited text no. 183
    
184.
Wiles CM, Clarke CR, Irwin HP, Edgar EF, Swan AV. Hyperbaric oxygen in multiple sclerosis: a double blind trial. Br Med J (Clin Res Ed). 1986;292:367-371.  Back to cited text no. 184
    
185.
Harpur GD, Suke R, Bass BH, et al. Hyperbaric oxygen therapy in chronic stable multiple sclerosis: double-blind study. Neurology. 1986;36:988-991.  Back to cited text no. 185
    
186.
Barnes MP, Bates D, Cartlidge NE, French JM, Shaw DA. Hyperbaric oxygen and multiple sclerosis: final results of a placebo-controlled, double-blind trial. J Neurol Neurosurg Psychiatry. 1987;50:1402-1406.  Back to cited text no. 186
    
187.
Kindwall EP, McQuillen MP, Khatri BO, Gruchow HW, Kindwall ML. Treatment of multiple sclerosis with hyperbaric oxygen. Results of a national registry. Arch Neurol. 1991;48:195-199.  Back to cited text no. 187
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In Vivo S...In Vitro ...
  In this article
Abstract
Introduction
Clinical Trials
Conclusion
References

 Article Access Statistics
    Viewed383    
    Printed0    
    Emailed0    
    PDF Downloaded92    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]