• The following list provides a 'knowledge share base' working to collaborate and promote the benefits of Hyperbaric Oxygen Therapy.

  • Australia is not a leader in this field but lagging behind the rest of the world in relationship to the wider applications of modern Hyperbaric Oxygen Therapy using different 'pressure protocols for different conditions'. 

  • The information provided does not constitute a medical endorsement or recommendation. It is intended for informational purposes only, and no claims, either real or implied, are being made. 

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity.

 * Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.


OXYMED provides HBOT combined with an integrative medical approach including Cytokine panel monitoring

Elevated pro-inflammatory markers Cytokines, Growth Factors, Interleukins are linked with chronic and progressive neurodegenerative disease - often referred to as a Cytokine Storm leading to multisystem inflammatory cascade.

  • TNFα combined with other pro-inflammatory Cytokines IL 1, 6, 8 often leads to chronic 'auto-immune' illness - the body attacks itself. 

  • Interleukin 6 (IL6) can increase up to a 1,000-fold during trauma and infection.

 * IL-6 is a growth and survival factor in human glioblastoma cells and plays an important role in malignant progression.


 * Hyperbaric Oxygen (HBO) UP~REGULATES Circulating Stem Cells (CD34+), Growth Factors (VEGF, BDNF, GDNF), Anti-inflammatory Interleukins including IL4, IL10, IL12, IL13 and INFγ (positive feedback loop).

 **  HBO DOWN~REGULATES Pro-inflammatory Interleukins IL1, IL6, IL8, TNFα, S100B.

 ** N-Acetyl Cysteine (NAC) is a TNFα blocker and down regulates pro-inflammatory interleukins including IL1, 6, 8.


J Neurochem. 2015 May 5. doi: 10.1111/jnc.13154. [Epub ahead of print]

Lack of TNF-alpha receptor type 2 protects motor neurons in a cellular model of amyotrophic lateral sclerosis and in mutant SOD1 mice but does not affect disease progression.

Tortarolo M1, Vallarola A, Lidonnici D, Battaglia E, Gensano F, Spaltro G, Fiordaliso F, Corbelli A, Garetto S, Martini E, Pasetto L, Kallikourdis M, Bonetto V, Bendotti C.

Author information

  • 1Laboratory of Molecular Neurobiology, Department of Neurosciences, IRCCS - Mario Negri Institute for Pharmacological Research, via La Masa 19, 20156, Milano, Italy.


Changes in the homeostasis of tumor necrosis factor α (TNFα) have been demonstrated in patients and experimental models of amyotrophic lateral sclerosis (ALS). However, the contribution of TNFα to the development of ALS is still debated. TNFα is expressed by glia and neurons and acts through the membrane receptors TNFR1 and TNFR2, which may have opposite effects in neurodegeneration. We investigated the role of TNFα and its receptors in the selective motor neuron death in ALS in vitro and in vivo. TNFR2 expressed by astrocytes and neurons, but not TNFR1, was implicated in motor neuron loss in primary SOD1-G93A co-cultures. Deleting TNFR2 from SOD1-G93A mice, there was partial but significant protection of spinal motor neurons, sciatic nerves and tibialis muscles. However, no improvement of motor impairment or survival was observed. Since the sciatic nerves of SOD1-G93A/TNFR2-/- mice showed high phospho-TDP-43 accumulation and low levels of acetyl-tubulin, two indices of axonal dysfunction, the lack of symptom improvement in these mice might be due to impaired function of rescued motor neurons. These results indicate the interaction between TNFR2 and membrane-bound TNFα as an innovative pathway involved in motor neuron death. Nevertheless, its inhibition is not sufficient to stop disease progression in ALS mice, underlining the complexity of this pathology.


Cell Rep. 2015 Apr 28;11(4):592-604. doi: 10.1016/j.celrep.2015.03.053. Epub 2015 Apr 16.

Astrocyte-Derived TGF-β1 Accelerates Disease Progression in ALS Mice by Interfering with the Neuroprotective Functions of Microglia and T Cells

Endo F1, Komine O2, Fujimori-Tonou N3, Katsuno M4, Jin S2, Watanabe S2, Sobue G5, Dezawa M6, Wyss-Coray T7, Yamanaka K8.

Author information

  • 1Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi 4648601, Japan; Laboratory for Motor Neuron Disease, RIKEN Brain Science Institute, Wako, Saitama 3510198, Japan; Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 9808575, Japan.

  • 2Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi 4648601, Japan.

  • 3Laboratory for Motor Neuron Disease, RIKEN Brain Science Institute, Wako, Saitama 3510198, Japan.

  • 4Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 4668550, Japan.

  • 5Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 4668550, Japan; CREST, Japan Science and Technology Agency, Saitama 3320012, Japan.

  • 6Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 9808575, Japan.

  • 7Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.

  • 8Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi 4648601, Japan; Laboratory for Motor Neuron Disease, RIKEN Brain Science Institute, Wako, Saitama 3510198, Japan; CREST, Japan Science and Technology Agency, Saitama 3320012, Japan. Electronic address:


Neuroinflammation, which includes both neuroprotective and neurotoxic reactions by activated glial cells and infiltrated immune cells, is involved in the pathomechanism of amyotrophic lateral sclerosis (ALS). However, the cytokines that regulate the neuroprotective inflammatory response in ALS are not clear. Here, we identify transforming growth factor-β1 (TGF-β1), which is upregulated in astrocytes of murine and human ALS, as a negative regulator of neuroprotective inflammatory response.

We demonstrate that astrocyte-specific overproduction of TGF-β1 in SOD1(G93A) mice accelerates disease progression in a non-cell-autonomous manner, with reduced IGF-I production in deactivated microglia and fewer T cells with an IFN-γ-dominant milieu. Moreover, expression levels of endogenous TGF-β1 in SOD1(G93A) mice negatively correlate with lifespan.

Furthermore, pharmacological administration of a TGF-β signaling inhibitor after disease onset extends survival time of SOD1(G93A) mice. These findings indicate that astrocytic TGF-β1 determines disease progression and is critical to the pathomechanism of ALS.


Hyperbaric oxygen preconditioning attenuates neuroinflammation after intracerebral hemorrhage in rats by regulating microglia characteristics.

Liming Yang Southwest Hospital Lawton | United States

Brain Res 2015 Nov 21;1627:21-30. Epub 2015 Aug 21.

Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address:

  • November 2015

Intracerebral Hemorrhage (ICH) results in a detrimental neurologic disorder with complicated secondary brain injury. Hyperbaric oxygen preconditioning (HBOP) may be a safe and effective therapeutic method for ICH victims. Our previous studies have demonstrated that HBOP induces neuroprotection in cerebral ischemia and traumatic brain injury. This study aimed to investigate whether HBOP could alleviate neuroinflammation by regulating changes in microglia characteristics in a rat model of ICH. ICH was induced by autologous arterial blood injection, and animals were sacrificed at 12, 24, and 72 h post injury. We measured motor function and brain water content to evaluate the extent of inflammation. Fluoro-Jade C and TNF-α staining was used to characterize neuronal degeneration and neuroinflammatory cytokines, and immunofluorescence staining was performed for CD11b to show activated microglia and Iba-1 to show microglia. Our results indicate that motor dysfunction and brain water content are alleviated by HBOP, and Fluoro-Jade C staining demonstrates that neuron degeneration decreased in the HBOP group. The growth of Iba-1-positive microglia decreased in the HBOP group. Moreover, TNF-α was dynamically reduced in the HBOP group compared with the ICH group. CD11b-Iba-1 double staining demonstrated that the ratio of CD11b and Iba-1 was significantly decreased in the HBOP group. Overall, the data demonstrated that HBOP could significantly alleviate the ICH-induced neuroinflammation by regulating microglia characteristics changing. The phenomenon may propel the progress of the relation between microglia and HBOP and represent a novel target for ICH treatment.

Neurobiol Dis. 2015 May 19. pii: S0969-9961(15)00171-0. doi: 10.1016/j.nbd.2015.05.009. [Epub ahead of print]

Iron accumulation promotes TACE-mediated TNF-α secretion and neurodegeneration in a mouse model of ALS

Lee JK1, Shin JH2, Gwag BJ3, Choi EJ4.

Author information

  • 1Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.

  • 2Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

  • 3GNT Pharma, Suwon, Korea.

  • 4Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea. Electronic address:


Oxidative stress contributes to degeneration of motor neurons in patients with amyotrophic lateral sclerosis (ALS) as well as transgenic mice overexpressing ALS-associated human superoxide dismutase 1 (SOD1) mutants. However, the molecular mechanism by which the ALS-linked SOD1 mutants including SOD1(G93A) induce oxidative stress remains unclear. Here, we show that iron was accumulated in ventral motor neurons from SOD1(G93A)-transgenic mice even at 4 weeks of age, subsequently inducing oxidative stress. Iron chelation with deferoxamine mesylate delayed disease onset and extended lifespan of SOD1(G93A) mice. Furthermore, SOD1(G93A)-induced iron accumulation mediated the increase in the enzymatic activity of TNF-α converting enzyme (TACE), leading to secretion of TNF-α at least in part through iron-dependent oxidative stress. Our findings suggest iron as a key determinant of early motor neuron degeneration as well as proinflammatory responses at symptomatic stage in SOD1(G93A) mice.

J Neuroinflammation. 2014 May 23;11:94. doi: 10.1186/1742-2094-11-94.

Evaluating the levels of interleukin-1 family cytokines in sporadic amyotrophic lateral sclerosis

Italiani P, Carlesi C, Giungato P, Puxeddu I, Borroni B, Bossù P, Migliorini P, Siciliano G, Boraschi D1.

Author information

  • 1Laboratory of Innate Immunity and Cytokines, Institute of Biomedical Technologies, National Research Council, Via G, Moruzzi 1, 56124 Pisa, Italy.



Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease leading to the death of affected individuals within years. The involvement of inflammation in the pathogenesis of neurodegenerative diseases, including ALS, is increasingly recognized but still not well understood. The aim of this study is to evaluate the levels of inflammation-related IL-1 family cytokines (IL-1β, IL-18, IL-33, IL-37) and their endogenous inhibitors (IL-1Ra, sIL-1R2, IL-18BP, sIL-1R4) in patients with sporadic ALS (sALS), METHODS: Sera were collected from 144 patients (125 patients were characterized by disease form, duration, and disability, using the revised ALS functional rating scale (ALSFRS-R) and from 40 matched controls. Cerebrospinal fluid (CSF) was collected from 54 patients with sALS and 65 patients with other non-infectious non-oncogenic diseases as controls. Cytokines and inhibitors were measured by commercial ELISA.


Among the IL-1 family cytokines tested total IL-18, its endogenous inhibitor IL-18BP, and the active form of the cytokine (free IL-18) were significantly higher in the sALS sera than in controls. No correlation between these soluble mediators and different clinical forms of sALS or the clinical setting of the disease was found. IL-18BP was the only mediator detectable in the CSF of patients.


Among the IL-1 family cytokines, only IL-18 correlates with this disease and may therefore have a pathological role in sALS. The increase of total IL-18 suggests the activation of IL-18-cleaving inflammasome. Whether IL-18 upregulation in circulation of sALS patients is a consequence of inflammation or one of the causes of the pathology still needs to be addressed.

J Clin Neurosci. 2013 Oct;20(10):1371-6. doi: 10.1016/j.jocn.2012.11.007. Epub 2013 Jul 10.

An immunohistochemical study of increased tumor necrosis factor-α in the skin of patients with amyotrophic lateral sclerosis

Fukazawa H1, Tsukie T, Higashida K, Fujikura M, Ono S.

Author information

  • 1Department of Neurology, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, Chiba 299-0111, Japan.


Tumor necrosis factor-α (TNF-α) is a major inflammatory cytokine that elicits a wide range of biological responses and is implicated in the pathogenesis of neurodegenerative diseases. Skin studies from patients with amyotrophic lateral sclerosis (ALS) have shown unique pathological and biochemical abnormalities. The lack of bedsore formation is considered characteristic of ALS. We undertook a quantitative immunohistochemical study of TNF-α in the skin from patients with ALS and controls with other neurologic or muscular diseases. Immunohistochemistry for TNF-α demonstrated cytoplasmic activity in the epidermis and in some blood vessels and glands. The proportion of TNF-α-positive (TNF-α+) cells in the epidermis in patients with ALS was significantly higher (p<0.001) than in controls. There was a significant positive relationship (r=0.87, p<0.001) between this proportion and duration of illness in patients with ALS, but there was no such relationship in control subjects. The optical density of TNF-α+ cells in the epidermis in patients with ALS was markedly higher (p<0.001) than in controls. There was a significant positive relationship (r=0.70, p<0.001) between the immunoreactivity and duration of illness in patients with ALS. However, there was no such relationship in controls. In addition, there was an appreciable positive correlation (r=0.59, p<0.01) in patients with ALS between the proportion of TNF-α+ cells and the optical density of these cells, but with no correlation in controls. These data suggest that changes in TNF-α identified in the skin of patients with ALS are likely to be related to the disease process and that metabolic alterations of TNF-α may take place in the skin of patients with ALS.


Biomed Res Int. 2014;2014:474296. doi: 10.1155/2014/474296. Epub 2014 Jul 3.

Ketogenic diet in neuromuscular and neurodegenerative diseases

Paoli A1, Bianco A2, Damiani E1, Bosco G1.

Author information

  • 1Department of Biomedical Sciences, University of Padova, Via Marzolo 3, 35031 Padova, Italy.

  • 2Sport and Exercise Sciences Research Unit, University of Palermo, Via Eleonora Duse 2, 90146 Palermo, Italy.


An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review.

PLoS One. 2014 Jul 25;9(7):e103526. doi: 10.1371/journal.pone.0103526. eCollection 2014.

Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model

Ari C1, Poff AM1, Held HE1, Landon CS1, Goldhagen CR1, Mavromates N1, D'Agostino DP1.

Author information

  • 1Department of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.


Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity.

The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.


J Neurotrauma. 2014 Aug 1;31(15):1343-53. doi: 10.1089/neu.2013.3222. Epub 2014 Jul 11.

Nrf2 activation in astrocytes contributes to spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning

Xu J1, Huang G, Zhang K, Sun J, Xu T, Li R, Tao H, Xu W.

Author information

  • 11 Department of Diving and Hyperbaric Medicine, College of Naval Medicine, the Second Military Medical University , Shanghai, China .


In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtime-polymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, γ-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury.

  • HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in neurons. In conclusion, our findings demonstrated that spinal cord ischemic tolerance induced by HBO-PC may be mainly related to Nrf2 activation in astrocytes.


Spinal Cord. 2011 Jun;49(6):749-53. doi: 10.1038/sc.2010.185. Epub 2011 Jan 18.

Conservative treatment with hyperbaric oxygen therapy for cervical spondylotic amyotrophy

Tofuku K1, Koga H, Yone K, Komiya S.

Author information



Small case series of patients with cervical spondylotic amyotrophy (CSA) managed by conservative treatment with hyperbaric oxygen (HBO) therapy.


To study the effects of conservative treatment with HBO therapy of CSA patients.


Department of Orthopaedic Surgery, Imakiire General Hospital, Kagoshima, Japan.


This study included 10 patients with CSA who underwent rehabilitation, including cervical traction and muscle exercise, for some period of time but did not respond well to it, and were then managed by additional HBO therapy for rehabilitation. Information was obtained on the duration of symptoms and strength of the most atrophic muscle, intramedullary high-signal-intensity changes on T2-weighted magnetic resonance imaging, presence of 'snake-eyes' appearance and the number of stenotic canal levels.


The mean duration of symptoms before HBO treatment was 3.1 months. The axial T2-weighted magnetic resonance images of all 10 patients showed a 'snake-eyes' appearance. The mean number of stenotic canal levels was 0.3. There was marked improvement on manual muscle testing from a mean of 1.9 pretreatment to a mean of 4.4 at the last follow-up after HBO therapy. The outcomes of all 10 patients, whose results were classified as excellent or good, were considered clinically satisfactory.


To our knowledge, conservative treatment with HBO therapy for CSA patients has not previously been described. It appears that HBO therapy might improve ischemic injury of the anterior horns in CSA patients with short duration of symptoms.


BMC Neurosci. 2006 Apr 3;7:29.

A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis

Zhao Z1, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM.

Author information

  • 1Neuroinflammation Research Laboratories, Department of Psychiatry, USA.



The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization.


SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-beta-3 hydroxybutyrate (DBH), has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047). In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH.


This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.


Amyotroph Lateral Scler Other Motor Neuron Disord 2004 Dec;5(4):250-4

Department of Neurology, University of Miami School of Medicine, Miami, FL 33136, USA.

  • December 2004

Background: Vascular endothelial growth factor and mitochondrial abnormalities have been described in ALS and its animal models. We have reported that hyperbaric oxygen (HBO) treatment delayed the onset of weakness in the wobbler mouse.

Objective: To perform a Phase I safety study of HBO in patients with ALS.
Methods: Five patients with ALS were treated for 60min with 100% oxygen at 2 atmospheres pressure daily for five days a week for four weeks. The patients reported any deterioration in their condition after each treatment, and their neurological condition was measured serially during the four weeks of the treatment, and for four further weeks.

Results: Four patients reported decreased fatigue, while one patient dropped out at three weeks because of increased fatigue. Maximum isometric voluntary contraction (MVIC) of all muscle groups except right hand grip improved significantly by up to 97%. Most improvement occurred during the four weeks after treatment. It is possible that the improvement in muscle strength was a placebo or a learning effect, though no such effects have been detected in prior therapeutic trials in ALS using MVIC. No change was detected in other measures of neuromuscular function.

Conclusions: A longer duration, placebo controlled trial in a larger number of patients is needed to determine the safety and efficacy of HBO. Until that is completed, it is not recommended that ALS patients should be treated with HBO.

Neuroscience. 2003;120(1):113-20.

Hyperbaric oxygen therapy protects against mitochondrial dysfunction and delays onset of motor neuron disease in Wobbler mice

Dave KR1, Prado R, Busto R, Raval AP, Bradley WG, Torbati D, Pérez-Pinzón MA.

Author information

  • 1Department of Neurology, D4-5, University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101, USA.


The Wobbler mouse is a model of human motor neuron disease. Recently we reported the impairment of mitochondrial complex IV in Wobbler mouse CNS, including motor cortex and spinal cord. The present study was designed to test the effect of hyperbaric oxygen therapy (HBOT) on (1) mitochondrial functions in young Wobbler mice, and (2) the onset and progression of the disease with aging.

HBOT was carried out at 2 atmospheres absolute (2 ATA) oxygen for 1 h/day for 30 days. Control groups consisted of both untreated Wobbler mice and non-diseased Wobbler mice. The rate of respiration for complex IV in mitochondria isolated from motor cortex was improved by 40% (P<0.05) after HBOT. The onset and progression of the disease in the Wobbler mice was studied using litters of pups from proven heterozygous breeding pairs, which were treated from birth with 2 ATA HBOT for 1 h/day 6 days a week for the animals' lifetime. A "blinded" observer examined the onset and progression of the Wobbler phenotype, including walking capabilities ranging from normal walking to jaw walking (unable to use forepaws), and the paw condition (from normal to curled wrists and forelimb fixed to the chest). These data indicate that the onset of disease in untreated Wobbler mice averaged 36+/-4.3 days in terms of walking and 40+/-5.7 days in terms of paw condition.

HBOT significantly delayed (P<0.001 for both paw condition and walking) the onset of disease to 59+/-8.2 days (in terms of walking) and 63+/-7.6 days (in terms of paw condition). Our data suggest that HBOT significantly ameliorates mitochondrial dysfunction in the motor cortex and spinal cord and greatly delays the onset of the disease in an animal model of motor neuron disease.