ALZHEIMER'S, DEMENTIA, COGNITIVE DECLINE

IMPROVES BRAIN METABOLISM IN ALZHEIMER’S DISEASE.

A 2019 brain imaging study involving SPECT and PET scans is the first to document improvements in brain metabolism in a patient with Alzheimer’s disease.

The subject of the study was a 58-year-old woman whose cognitive function had been declining for 5 years.

 * She underwent 40 sessions of HBOT.

After just 21 sessions, she reported better moods, a boost in energy, and better ability to perform routine tasks. She even said it was easier to do the crossword puzzle.   ** After 40 sessions of HBOT, she reported improvements in concentration, memory, sleep, and ability to use the computer. She also noted a decrease in disorientation, less frustration, and her anxiety was gone.

The brain scans showed 6.5-38% improvement in overall brain metabolism, prompting the researchers to suggest HBOT could be a potential therapy for Alzheimer’s patients. “We demonstrated the largest improvement in brain metabolism of any therapy for Alzheimer’s disease,” says the lead study author Dr. Paul Harch. “HBOT in this patient may be the first treatment not only to halt, but temporarily reverse disease progression in Alzheimer’s disease.”

Figure - T1-weighted coronal images approximately at the same level showing hippocampal atrophy in the 86-year-old patient with a clinical diagnosis of Alzheimer's disease and the 14-year-old patient with severe traumatic brain injury (TBI).

Note compared to the control coronal image on the right, both the TBI case and the Alzheimer's exhibit hippocampal atrophy, ventricular dilation and sulcal widening.

(Bottom) All images are 3-D renderings from volume acquisition magnetic resonance imaging (MRI) depicting the dorsal view of the brain in each subject described above. Note the similarity of the diffuse pattern of atrophic change that has occurred in both the patient with Alzheimer's disease and the adolescent who survived severe TBI.

Clearly, the elderly patient with Alzheimer's has more severe atrophy but nonetheless the atrophy in the TBI adolescent is substantial, especially when compared to the typical developing adolescent control.

 

Note: The patient with Alzheimer's disease is taken from Jacobson et al. (2009); this patient's clinical findings, including additional neuroimaging and neuropsychological details are described in that publication. (Reproduced with permission from John Wiley and Sons).

Hyperbaric Oxygen Therapy DRIVES Functional Recovery & Neuroplasticity

Hyperbaric oxygen therapy as a new treatment approach for Alzheimer's disease - full pdf

Neural Regen Res 2018 May;13(5):817-818

Ronit Shapira Tel Aviv University Israel,  Shai Efrati Tel Aviv University Israel

Department of Neurobiology, the George S. Wise Faculty of Life Sciences; Sagol School of Neuroscience, Tel Aviv University, Israel.

  • May 2018

Hyperbaric oxygen therapy as a new treatment approach for Alzheimer’s disease (AD): Alongside the increase in life expectancy, the prevalence of age-related disorders, such as neurodegenerative diseases, is on the rise. For example, AD, the most common form of dementia in the elderly, accounts for 60–80% of all dementia cases. However, there is presently no cure for this disease and no effective treatment that would slow disease progression despite billions of dollars invested in drug development. As AD is a complex disease, the development of effective and specific drugs is difficult. Thus, examining alternative treatments that target several disease-related pathways in parallel is of the utmost importance.

Hyperbaric oxygen treatment (HBOT) is the medical administration of 100% oxygen at environmental pressure greater than 1 atmosphere absolute (ATA). HBOT has been shown to improve neurological functions and life quality following neurological incidents such as stroke and traumatic brain injury, and to improve performance of healthy subjects in multitasking. The current perspective describes a recent study demonstrating that HBOT can ameliorate AD-related pathologies in an AD mouse model, and provides unique insights into HBOT’s mechanisms of action. Old triple-transgenic model (3xTg)-AD mice were exposed to 14 days of HBOT and showed reduced hypoxia and neuroinflammation, reduction in beta-amyloid (Aβ) plaques and phosphorylated tau, and improvement in behavioral tasks. This and additional studies have shown that cerebral ischemia is a common denominator in many of the pathological pathways and suggests that oxygen is an important tool in the arsenal for our fight against AD.

Given that HBOT is used in the clinic to treat various neurological conditions, we suggest that this approach presents a new platform for the treatment of AD. 
 

Alzheimers Dement. 2018 Aug 8. pii: S1552-5260(18)33035-8. doi: 10.1016/j.jalz.2018.06.2857. [Epub ahead of print]

Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults.

Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders.

METHODS:

Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index ≥9. Linear regression examined changes in Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline.

RESULTS:

Mean age was 70 years, mean Mini-Mental State Examination was 27, and BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive decline (P = .015). Cerebrospinal fluid soluble intercellular adhesion molecule, vascular endothelial growth factor, interleukin-8, serum amyloid A, macrophage derived chemokine, and gender generated an area under the curve of 0.95. Serum interleukin-16, vascular endothelial growth factor-D, interleukin-15, and other variables generated an area under the curve of 0.92.

DISCUSSION:

BBB breakdown is associated with cognitive decline. Cell adhesion, neutrophil migration, high-density lipoprotein metabolism, and angiogenesis are implicated.

Hyperbaric oxygen therapy ameliorates pathophysiology of 3xTg-AD mouse model by attenuating neuroinflammation.

Shai Efrati - Tel Aviv University

​Neurobiol Aging 2018 Feb 20;62:105-119. Epub 2017 Oct 20.

Department of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address:

​There is a real need for new interventions for Alzheimer's disease (AD). Hyperbaric oxygen therapy (HBOT), the medical administration of 100% oxygen at conditions greater than 1 atmosphere absolute, has been used successfully to treat several neurological conditions, but its effects on AD pathology have never been thoroughly examined. Therefore, we exposed old triple-transgenic (3xTg) and non-transgenic mice to HBOT followed by behavioral, histological, and biochemical analyses. HBOT attenuated neuroinflammatory processes by reducing astrogliosis, microgliosis, and the secretion of proinflammatory cytokines (IL-1β and TNFα) and increasing expression of scavenger receptor A, arginase1, and antiinflammatory cytokines (IL-4 and IL-10).

  • Moreover, HBOT reduced hypoxia, amyloid burden, and tau phosphorylation in 3xTg mice and ameliorated their behavioral deficits. Therefore, we suggest that HBOT has multifaceted effects that reduce AD pathologies, even in old mice. Given that HBOT is used in the clinic to treat various indications, including neurological conditions, these results suggest HBOT as a novel therapeutic intervention for AD.

5 December 2017

Hyperbaric Oxygen Treatments may ameliorate symptoms experienced by patients with Alzheimer's disease

A new Tel Aviv University study reveals that hyperbaric oxygen treatments may ameliorate symptoms experienced by patients with Alzheimer's disease.

"This revolutionary treatment for Alzheimer's disease uses a hyperbaric oxygen chamber, which has been shown in the past to be extremely effective in treating wounds that were slow to heal," says Prof. Uri Ashery of TAU's Sagol School of Neuroscience and the Faculty of Life Sciences, who led the research for the study.

 

"We have now shown for the first time that hyperbaric oxygen therapy can actually improve the pathology of Alzheimer's disease and correct behavioral deficits associated with the disease. "This research is extremely exciting as it explores a new therapy that holds promise as a treatment of Alzheimer's disease," Prof. Ashery says.

 

The research was conducted by PhD student Ronit Shapira of TAU's Faculty of Life Sciences; Prof. Beka Solomon and Dan Frenkel of TAU's Sagol School of Neuroscience and Faculty of Life Sciences; and Prof. Shai Efrati of TAU's Sackler Faculty of Medicine, Sagol School of Neuroscience and Assaf-Harofeh Medical Center. It was published in the journal Neurobiology of Aging.

 

Patients who undergo hyperbaric oxygen therapy for different conditions breathe in pure oxygen in a pressurized room or chamber. In this chamber, the air pressure is increased to twice that of normal air. Under these conditions, oxygen solubility in the blood increases and is transported by blood vessels throughout the body. The added oxygen stimulates the release of growth factors and stem cells, which themselves promote healing.

The TAU scientists used a mouse model of Alzheimer's disease and built a custom-made hyperbaric oxygen chamber suitable for small animals. Then, over the course of 14 days, the team administered hyperbaric oxygen treatment to the mice for one hour per day. After 14 days, the mice underwent a series of behavioral tests as well as tissue biochemical tests to understand how hyperbaric oxygen treatment affects the pathological hallmarks associated with Alzheimer's disease.

 

 * "The treatment reduced behavioral deficiencies compared to the non-transgenic control mice, reduced plaque pathology by 40%, and reduced neuroinflammation by about 40%."

The treatment reduced behavioral deficiencies compared to the non-transgenic control mice, reduced plaque pathology by 40%, and reduced neuroinflammation by about 40%. "There are serious clinical implications to this research," says Shapira, principal investigator of the study. "Hyperbaric oxygen treatment is a well-tolerated and safe therapy used in clinics around the world for various medical conditions, including neurological disorders. Although further research is needed to elucidate the 6/2017 Hyperbaric oxygen therapy may alleviate symptoms of Alzheimer's Disease:

Treatment has potential to correct behavioral and physical defi… https://www.sciencedaily.com/releases/2017/12/171205120013.htm 2/3

 

American Friends of Tel Aviv University. "Hyperbaric oxygen therapy may alleviate symptoms of Alzheimer's Disease". Treatment has potential to correct behavioral and physical deficits associated with the disease."

 

ScienceDaily. ScienceDaily, 5 December 2017. . "In this hallmark study, the beneficial physiological effects of hyperbaric oxygen therapy were directly demonstrated on Alzheimer-affected brain tissue," says Prof. Efrati. "We assume that the main challenge in human use will be to initiate the treatment at early stages before significant amount of brain tissue is lost."

 

The researchers are currently testing the effectiveness of hyperbaric oxygen treatment on an additional mouse model of Alzheimer's disease to investigate the mechanisms underlying its impact on the disease.

Story Source: Materials provided by American Friends of Tel Aviv University. Note: Content may be edited for style and length. Journal Reference: 1. Ronit Shapira, Beka Solomon, Shai Efrati, Dan Frenkel, Uri Ashery. Hyperbaric oxygen therapy ameliorates pathophysiology of 3xTg-AD mouse model by attenuating neuroinflammation. Neurobiology of Aging, 2018; 62: 105 DOI: 10.1016/j.neurobiolaging.2017.10.007

Yonsei Med J. 2017 Jan;58(1):131-138. doi: 10.3349/ymj.2017.58.1.131.

Hyperbaric Oxygen Pretreatment Improves Cognition and Reduces Hippocampal Damage Via p38 Mitogen-Activated Protein Kinase in a Rat Model.

To investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer's disease (AD) rat model.

MATERIALS AND METHODS:

Rats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)₁₋₄₀ was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ₁₋₄₀ injection. Learning and memory capabilities were examined using the Morris water maze task. Neuronal damage and astrocyte activation were evaluated by hematoxylin-eosin staining and immunohistochemistry, respectively. Dendritic spine density was determined by Golgi-Cox staining. Tumor necrosis factor-α, interleukin-1β, and interleukin-10 production was assessed by enzyme-linked immunosorbent assay. Neuron apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Protein expression was examined by western blotting.

RESULTS:

Learning and memory dysfunction was ameliorated in the HBO+AD group, as shown by significantly lower swimming distances and escape latency, compared to the AD group. Lower rates of neuronal damage, astrocyte activation, dendritic spine loss, and hippocampal neuron apoptosis were seen in the HBO+AD than in the AD group. A lower rate of hippocampal p38 mitogen-activated protein kinase (MAPK) phosphorylation was observed in the HBO+AD than in the AD group.

CONCLUSION:

HBO pretreatment improves cognition and reduces hippocampal damage via p38 MAPK in AD rats.

60-daily sessions of Hyperbaric Oxygenation (1.5 ATA 100% O2 for 60-minutes) Induces Neuroplasticity and Improves Cognition Years After Anoxic Brain Injury Due To Cardiac Arrest.

Restor Neurol Neurosci. 2015 Aug 19;33(4):471-86. doi: 10.3233/RNN-150517.

 

Author information

Hadanny A 1,2, Golan H 2,3, Fishlev G 1,2, Bechor Y 1, Volkov O 2,3, Suzin G 1, Ben-Jacob E 4,5,6, Efrati S 1,2,4,5.

1. Sagol Center for Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Zerifin, Israel. 2. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 3. Nuclear Imaging Division, Assaf Harofeh Medical Center, Zerifin, Israel. 4. Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel. 5. Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel. 6. School of Physics and Astronomy, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv, Israel.

Abstract

Cognitive impairment may occur in 42-50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest.

 

Methods

Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging.

 

Results

The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5-7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. The treatment was well tolerated and all patients completed the treatment protocol. No significant adverse reactions were recorded in any of the patients.

'Hyperbaric Oxygenation is a potent mean of delivering sufficient Oxygen to the brain for repair processes and induction of neuroplasticity'. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging.

 

Case 1: 52-year-old male, one year post ventricular fibrillation, suffering from ataxia and significant cognitive decline.

Baseline cognitive evaluation showed a very low memory index score and low executive function, verbal function, information processing speed, attention, and motor skills index scores.

After 60 HBO2 sessions, the patient had improvements in verbal function, executive function and attention from scores of 71, 73 and 68 to 106, 90 and 81, respectively. Improvement was also seen in memory from 25 to 43, yet the score was still low. Clinically, with regards to his ADL after HBO2, the patient was able to participate in housework, managing finances and shopping.

Brain SPECT evaluation showed the that the largest post HBO2 increase in brain activity was in the perirhinal cortex (BA 36) with over 50% increase, in the primary visual cortex (BA 17,18) with over 30% increase and in the cingulate gyrus (BA 23, 31) with over 20% increase (Fig. 4).

Case 2: 48-year-old male, 2 years post resuscitation, suffering from motordysphasia, left-right disorientation and significant cognitive dysfunction

Cognitive evaluation at baseline showed low memory, visual spatial and executive function scores in addition to low attention and motor scores.

After 60 HBO2 sessions, the patient had improvement in memory, visual spatial and executive function from scores of 58, 70 and 74 to 68, 76 and 79, respectively. Clinically, he had complete resolution of dysphasia. Improvements were also noticed in ADL abilities such as ability to do laundry and manage finances. Additionally, he was able to return to his previous work.

Brain SPECT evaluation showed the largest post HBO2 increase in the parietal lobes (BA 5,7), temporal lobe with over 25% increase, in the inferior orbital gyrus (BA 45,47), cingulate gyrus (BA 23,24), in Wernike’s area (BA 39) and in the primary visual cortex (BA 17,18) with over 15% increase (Fig. 5). 

Discussion

' * The most significant measurable improvements were in executive function, attention and memory'

The neurotherapeutic effects of HBO2 in patients suffering from CCI caused by cardiac arrest mediated anoxic brain injury, were evaluated by both clinical and brain imaging measures. Even though the acute injury was 5 months to 7.5 years (mean 31.3±7.7 months) prior to treatment, HBO2 was associated with significant cognitive improvement in all patients. The clinical improvements were well documented by neurocognitive tests and correlated with improved ability to perform the activities of daily living and quality of life. The most significant measurable improvements were in executive function, attention and memory.

Important validation and clues for future, larger scale studies were provided by the SPECT brain imaging. We found the clinical improvement to be well correlated with increased activity in the relevant brain area. More specifically, the brain areas that had the most significant increase in metabolic activation were in the perirhinal cortex (BA36), the pre-frontal cortex (BA 8,9,10,11), inferior frontal gyrus (BA 45,47), the anterior cingulate gyrus (BA 23,24) and the parietal lobes (BA 5,7).

A good correlation was found between the improved neurocognitive functions and the brain areas corresponding to these functions:

The perirhinal cortex activation after HBO2 was most prominent in patients that had significant memory improvement. The perirhinal cortex has a critical role in object recognition memory while interacting with the hippocampus (Brown & Aggleton, 2001).

Because the memory assessments in the cognitive tests were indeed recognition tasks, this area might be expected to be involved.

 

The pre-frontal cortex (BA10,11) and, more specifically, the inferior frontal gyrus (BA 45, 47) activation after HBO2 were prominent in all patients with significant executive function improvements. The right frontal gyrus is known to mediate a go/no go task (Aron, Robbins, & Poldrack, 2004), which was among the executive function tests used in the present study. The prefrontal gyrus is presumed to act as a filtering system that enhances goal directed activities and inhibits irrelevant activations. This filtering mechanism enables executive control (Miller&Cohen, 2001).  

The anterior cingulate gyrus (BA23, 24) activation after HBO2 was seen in the subjects with attention improvement. The anterior cingulate gyrus is presumed to be involved in error detection, especially in a Stroop task (Bush, Luu, & Posner, 2000), which was used in the attention tests. Lesions in this area can cause inattention to akinetic mutism (Bush et al., 2000).  

The posterior parietal lobes are involved in visual spatial processing. Lesions in the right parietal lobe are known to cause visual spatial construction deficits (Mishkin & Ungerleider, 1982). Activations of these areas were seen in the patients with visual-spatial index improvement.

The changes revealed by inspection of the pre and post SPECT images indicate that HBO2 can induce reactivation of neuronal activity in stunned areas in agreement with earlier studies (Barrett, 1998; Churchill et al., 2013; Jacobs et al., 1969).

  • This implies that increasing the plasma dissolved oxygen with hyperbaric oxygenation is a potent mean of delivering sufficient oxygen to the brain for repair processes and induction of neuroplasticity.

  • 'Any significant improvement after 5 months may be attributed to the intervention used'

 

This study has several limitations. The major one relates to the retrospective methodology and the relatively small number of patients. Still, the findings presented here are in agreement with and reinforce similar findings from previous prospective controlled trials in which the neuroplasticity effects of HBO2 ere demonstrated in chronic stages of other brain related injuries (Boussi-Gross et al., 2013). 'Hyperbaric Oxygenation can induce neuroplasticity at chronic stages in areas with metabolic dysfunction'.

Moreover, the natural history of anoxic brain injury implies that maximal recovery is expected during the first 3 months, and no further significant improvement is expected after 3 months (Lim et al., 2014). Accordingly, any significant improvement after 5 months may be attributed to the intervention used.

Although significant clinical improvement at a relatively late chronic stage and high correlation with the improved metabolic activity support the validity of the findings, larger randomized prospective controlled trials are needed.

Another important limitation relates to the HBO2 protocol. Although significant neurotherapeutic effects were achieved with 60 sessions of 1.5 ATA for 60 minutes, the exact protocol needed to induce maximal neuroplasticity with minimal side effects remains unknown. There is cumulative data that even smaller increase in pressure might be as effective (Efrati & Ben-Jacob, 2014).

As stated above, further randomized controlled trials with large patient cohorts are needed to better understand who the best candidates are and what the optimal HBO2 protocol is for patients suffering from ABI.

 

Conclusions

'Due to the growing numbers of cardiac arrest survivors, the application of HBO2 in this population should be considered'

Hyperbaric oxygen therapy may improve cognitive functions even during the late chronic phase after ABI resulting from cardiac arrest. Due to the growing numbers of cardiac arrest survivors, the application of HBO2 in this population should be considered. Further prospective randomized clinical studies should be carried out in order to evaluate the patients who can benefit the most from the treatment and the optimal HBO2 protocol (dose and duration) for this population.

Hyperbaric Oxygen Improves Post Concussion Syndrome Years After Traumatic Brain Injury (TBI)

Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial. PLoS ONE 8(11): e79995. doi:10.1371/journal.pone.0079995. Published November 15, 2013.

Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging.

The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments.

Methods and Findings: The trial population included 56 mTBI patients 1–5 years after injury with prolonged postconcussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT (60-minute) sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions.

The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. ‘‘Mindstreams’’ was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging.

Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements.

Conclusions: HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage.

Page 11 - Linking elevated oxygen, metabolism and brain activity to neuroplasticity

  • The changes in SPECT images after treatment indicate that HBOT led to reactivation of neuronal activity in stunned areas that seemed normal under CT and MRI imaging.

  • While SPECT imaging has a limited spatial resolution (compared, for example, to fMRI, the changes in activity were sufficiently robust to be clearly detected by the SPECT images. Recently, Kan et al. [57] discussed the need for potent interventions, such as elevated tissue oxygen, capable of repairing microenvironment alterations after mTBI (e.g impairments in vascular changes, in cerebral blood flow and in perfusion), leading to reduced oxygen availability followed by reduced metabolism, which in turn leads to reduced neuronal activity, loss of synapses and tampered neuronal connectivity.

  • The observed reactivation of neuronal activity in the stunned areas found here, along with similar results in post-stroke patients [3], imply that increasing the plasma oxygen concentration with hyperbaric oxygenation is a potent means of delivering to the brain sufficient oxygen for tissue repair. HBOT might initiate a cellular and vascular repair mechanism and improve cerebral vascular flow [34,58,59,60]. More specifically, HBOT induces regeneration of axonal white matter [61,62,63,64, has positive effect upon the myelinization and maturation of injured neural fibers [65], and can stimulate axonal growth and increase the ability of neurons to function and communicate with each other [66].

  • In addition, HBOT was found to have a role in initiation and/or facilitation of angiogenesis and cell proliferation processes needed for axonal regeneration [67]. At the cellular level, HBOT can improve cellular metabolism, reduce apoptosis, alleviate oxidative stress and increase levels of neurotrophins and nitric oxide through enhancement of mitochondrial function (in both neurons and glial cells). Moreover, the effects of HBOT on neurons can be mediated indirectly by glial cells, including astrocytes [23]. HBOT may promote the neurogenesis of endogenous neural stem cells [24]. With regard to secondary injury mechanisms in mTBI, HBOT can initiate vascular repair mechanism and improve cerebral vascular flow [58,59,68,69], promote blood brain barrier integrity and reduce inflammatory reactions [28] as well as brain edema [20,21,22,26,34,70].

  • A drawback to the above-mentioned findings is that the different effects have been tested at different experimental setups and while utilizing different protocols of HBOT. However, it is well noticed that there is at least one common denominator to all repair/regeneration mechanisms: Figure 6. Assessments of the mean relative changes and standard errors in quality of life measurements. The changes are shown for the crossover group following control period (green bars) and following HBOT (blue bars), and for the treated group following HBOT (red bars). Note that, according to the questionnaire structure, in the EQ-5D measurement improvement is reflected as score decrease, hence the negative values of change they are all energy/oxygen dependent. It might be possible that HBOT enables the metabolic change simply by supplying the missing energy/oxygen needed for those regeneration processes.

Clinical Research Supporting

 

Restor Neurol Neurosci. 2015 Aug 19;33(4):471-86. doi: 10.3233/RNN-150517.

Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage

Hadanny A1,2, Golan H2,3, Fishlev G1,2, Bechor Y1, Volkov O2,3, Suzin G1, Ben-Jacob E4,5,6, Efrati S1,2,4,5.

Author information

  • 1Sagol Center for Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Zerifin, Israel.

  • 2Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

  • 3Nuclear Imaging Division, Assaf Harofeh Medical Center, Zerifin, Israel.

  • 4Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel.

  • 5Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.

  • 6School of Physics and Astronomy, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv, Israel.

Abstract

PURPOSE:

Cognitive impairment may occur in 42-50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest.

METHODS:

Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging.

RESULTS:

The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5-7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging.

CONCLUSIONS:

Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event.

Undersea Hyperb Med. 2015 Jul-Aug;42(4):333-51.

Clinical results in brain injury trials using HBO2 therapy: Another perspective

Figueroa XA, Wright JK.

Abstract

The current debate surrounding the use of hyperbaric oxygen (HBO2) for neurological indications, specifically mild to moderate chronic traumatic brain injury (mTBI) and post-concussion syndrome (PCS), is mired in confusion due to the use of non-validated controls and an unfamiliarity by many practitioners of HBO2 therapy with the experimental literature.

In the past 40 years, the use of an air sham (21% oxygen, 1.14-1.5 atmospheres absolute/atm abs) in clinical and animal studies, instead of observational or crossover controls, has led to false acceptance of the null hypothesis (declaring no effect when one is present), due to the biological activity of these "sham" controls.

The recent Department of Defense/Veterans Administration (DoD/VA) sponsored trials, previous published reports on the use of HBO2 therapy on stroke and mTBI and preliminary reports from the HOPPS Army trial, have helped to highlight the biological activity of pressurized air, validate the development of a convincing control for future studies and demonstrate the effectiveness of a hyperbaric intervention for mTBI/ PCS.

Approval of HBO2 for neurological indications, especially for mTBI/PCS, should be granted at the federal, state and certifying body levels as a safe and viable treatment for recovery in the post-acute phase.

 

Hyperbaric Oxygen Therapy Induces Neuroplasticity in Chronic Stroke Victims

A prospective, randomized, controlled trial including 74 patients (15 were excluded). All participants suffered a stroke 6–36 months prior to inclusion and had at least one motor dysfunction. After inclusion, patients were randomly assigned to "treated" or "cross" groups. Brain activity was assessed by SPECT imaging; neurologic functions were evaluated by NIHSS, ADL, and life quality. Patients in the treated group were evaluated twice: at baseline and after 40 HBOT sessions. Patients in the cross group were evaluated three times: at baseline, after a 2-month control period of no treatment, and after subsequent 2-months of 40 HBOT sessions. HBOT protocol: Two months of 40 sessions (60-hours), 5 days/ week, 90 minutes each, 100% oxygen at 2 ATA.

  • We found that the neurological functions and life quality of all patients in both groups were significantly improved following the HBOT sessions while no improvement was found during the control period of the patients in the cross group.

  • Results of SPECT imaging were well correlated with clinical improvement. Elevated brain activity was detected mostly in regions of live cells (as confirmed by CT) with low activity (based on SPECT) – regions of noticeable discrepancy between anatomy and physiology.

  • Conclusions: The results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages. The observed clinical improvements imply that neuroplasticity can still be activated long after damage onset in regions where there is a brain SPECT/CT (anatomy/physiology) mismatch.

J Phys Ther Sci. 2015 May;27(5):1295-7. doi: 10.1589/jpts.27.1295. Epub 2015 May 26.

The effects of combined hyperbaric oxygen therapy on patients with post-stroke depression.

Yan D1, Shan J1, Ze Y1, Xiao-Yan Z1, Xiao-Hua H1.

Author information

1Department of Rehabilitation Medicine, Hangzhou Hospital of Zhejiang CAPF, China.

Abstract

[Purpose] To observe the effect of combined hyperbaric oxygen therapy on patients with post-stroke depression. [Subjects] Ninety patients with post-stroke depression were randomly divided into 3 groups: fluoxetine treatment group (n = 30), hyperbaric oxygen therapy group (n = 30), and hyperbaric oxygen combined treatment group (n = 30). [Methods] Fluoxetine treatment group received anti-depression drugs (fluoxetine, 20 mg/day), hyperbaric oxygen therapy group received hyperbaric oxygen (once a day, 5 days/week), hyperbaric oxygen combined treatment group received fluoxetine and hyperbaric oxygen treatments as described above. All patients received routine rehabilitation therapy. Hamilton Depression Scale (HAMD), and Scandinavian Stroke Scale (SSS) scores were evaluated before and at the end of 4th week. The total effective rate of depression release between the 3 groups was also compared at the end of study.

[Results] The end scores of HAMD and SSS in the 3 groups were significantly lower than those before treatment. The total effective rate of combined hyperbaric oxygen therapy group after treatment was higher than the other two groups.

  • Combined hyperbaric oxygen therapy plays an important role in the treatment of patients with post-stroke depression. The total effective rate of combined hyperbaric oxygen therapy was higher than other routine anti post-stroke depression treatments.

 

Neuropsychology. 2014 Nov 10. [Epub ahead of print]

Improvement of Memory Impairments in Poststroke Patients by Hyperbaric Oxygen Therapy

Boussi-Gross R, Golan H, Volkov O, Bechor Y, Hoofien D, Schnaider Beeri M, Ben-Jacob E, Efrati S.

Objective: Several recent studies have shown that hyperbaric oxygen (HBO2) therapy carry cognitive and motor therapeutic effects for patients with acquired brain injuries. The goal of this study was to address the specific effects of HBO2 on memory impairments after stroke at late chronic stages. Method: A retrospective analysis was conducted on data of 91 stroke patients 18 years or older (mean age ∼60 years) who had either ischemic or hemorrhagic stroke 3-180 months before HBO2 therapy (M = 30-35 months).

The HBO2 protocol included 40 to 60 daily sessions, 5 days per week, 90 min each, 100% oxygen at 2ATA, and memory tests were administered before and after HBO2 therapy using NeuroTrax's computerized testing battery. Assessments were based on verbal or nonverbal, immediate or delayed memory measures. The cognitive tests were compared with changes in the brain metabolic state measured by single-photon emission computed tomography.

 

  • Results revealed statistically significant improvements (p < .0005, effect sizes medium to large) in all memory measures after HBO2 treatments. The clinical improvements were well correlated with improvement in brain metabolism, mainly in temporal areas.

  • Conclusions: Although further research is needed, the results illustrate the potential of HBO2 for improving memory impairments in poststroke patients, even years after the acute event. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

 

J Formos Med Assoc. 2014 Sep;113(9):620-8. doi: 10.1016/j.jfma.2014.03.012. Epub 2014 Apr 29.

Repetitive hyperbaric oxygen therapy provides better effects on brain inflammation and oxidative damage in rats with focal cerebral ischemia.

Chen LF1, Tian YF2, Lin CH3, Huang LY4, Niu KC4, Lin MT5.

Abstract

BACKGROUND/PURPOSE:

Repetitive hyperbaric oxygen (HBO2) therapy may cause excessive generation of reactive oxygen species. This study assessed whether repetitive or 2-4-day trials of HBO2 therapy (2 treatments daily for 2-4 consecutive days) provides better effects in reducing brain inflammation and oxidative stress caused by middle cerebral artery occlusion (MCAO) in rats than did a 1-day trial of HBO2 therapy (2 treatments for 1 day).

METHODS:

Rats were randomly divided into four groups: sham; MCAO without HBO2 treatment; MCAO treated with 1-day trial of HBO2; and MCAO treated with 2-4-day trials of HBO2. One treatment of HBO2 (100% O2 at 253 kPa) lasted for 1 hour in a hyperbaric chamber.

RESULTS:

Therapy with the 2-4-day trials of HBO2 significantly and dose-dependently attenuated the MCAO-induced cerebral infarction and neurological deficits more than the 1-day trial of HBO2 therapy. The beneficial effects of repetitive HBO2 therapy were associated with: (1) reduced inflammatory status in ischemic brain tissues (evidenced by decreased levels of tumor necrosis factor-α, interleukin-1β, and myeloperoxidase activity); (2) decreased oxidative damage in ischemic brain tissues (evidenced by decreased levels of reactive oxygen and nitrogen species, lipid peroxidation, and enzymatic pro-oxidants, but increased levels of enzymatic antioxidant defenses); and (3) increased production of an anti-inflammatory cytokine, interleukin-10.

CONCLUSION:

The results provide the apparently contradictory finding that heightened oxygen tension reduced oxidative stress (and inflammation), which was reflected by increased antioxidant and decreased oxidant contents under focal cerebral ischemia.

Mol Neurobiol. 2014 Oct 30. [Epub ahead of print]

Combination of HBO and Memantine in Focal Cerebral Ischemia: Is There a Synergistic Effect?

Wang F1, Liang W, Lei C, Kinden R, Sang H, Xie Y, Huang Y, Qu Y, Xiong L.

Author information

  • 1Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China, fengwang515@gmail.com.

Abstract

Hyperbaric oxygen (HBO) therapy and memantine, a non-competitive NMDA antagonist, are both promising treatment strategies for improving stroke prognosis. However, HBO's narrow therapeutic time window (<6 h post-stroke) and the adverse effect of high-dose MEM administration limits the use of these therapeutic interventions. In this study, we investigated whether or not MEM could prolong the narrow therapeutic window of HBO treatment. Transient focal cerebral ischemia was induced in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 120 min. MCAO produced neurobehavioral deficits, increased infarction volume, increased Evans blue (EB) content and levels of pro-inflammatory factors, as well as depleted glutathione (GSH), and reduced catalase (CAT) and superoxide dismutase (SOD) activity in the ischemic ipsilateral hemisphere. The combination of 5 mg/kg MEM treatment 15 min after the onset of ischemic event and HBO therapy 12 h post-reperfusion significantly restored neurologic scores, EB concentration and IL-10 levels, as well as significantly decreased infarct volume and increased antioxidant activity. These results imply that the combination of MEM and HBO therapy not only prolongs the therapeutic window of HBO treatment, but also lowers the dosage requirement of MEM. The mechanism underlying the neuroprotective effects of the combined treatment may lie in alleviated blood-brain barrier (BBB) permeability, inhibited inflammatory response, and up-regulation of the antioxidant enzyme activity.

 

 

Cochrane Database Syst Rev. 2014 Nov 12;11:CD004954. [Epub ahead of print]

Hyperbaric oxygen therapy for acute ischaemic stroke

Bennett MH1, Weibel S, Wasiak J, Schnabel A, French C, Kranke P.

Author information

  • 1Department of Anaesthesia, Prince of Wales Hospital, Barker Street, Randwick, NSW, Australia, 2031.

Abstract

BACKGROUND:

Most cases of stroke are caused by impairment of blood flow to the brain (ischaemia), which results in a reduction in available oxygen and subsequent cell death. It has been postulated that hyperbaric oxygen therapy (HBOT) may reduce the volume of brain that will die by greatly increasing available oxygen, and it may further improve outcomes by reducing brain swelling. Some centres are using HBOT routinely to treat people with stroke. This is an update of a Cochrane Review first published in 2005.

OBJECTIVES:

To assess the effectiveness and safety of adjunctive HBOT in the treatment of people with acute ischaemic stroke.

SEARCH METHODS:

We searched the Cochrane Stroke Group Trials Register (last searched April 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (April 2014), MEDLINE (1966 to April 2014), EMBASE (1980 to April 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to April 2014), the Database of Randomised Controlled Trials in Hyperbaric Medicine (DORCTIHM) (searched April 2014) and the reference lists of articles. We handsearched relevant publications and contacted researchers to identify additional published and unpublished studies.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) that compared the effects of adjunctive HBOT versus those of no HBOT (no treatment or sham).

DATA COLLECTION AND ANALYSIS:

Three review authors independently extracted data, assessed each trial for internal validity and resolved differences by discussion.

MAIN RESULTS:

We included 11 RCTs involving 705 participants. The methodological quality of the trials varied. We could pool data only for case fatalities. No significant differences were noted in the case fatality rate at six months in those receiving HBOT compared with the control group (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.34 to 2.75, P value 0.96). Four of 14 scale measures of disability and functional performance indicated improvement following HBOT, for example, the mean Trouillas Disability Scale score was lower with HBOT (mean difference (MD) 2.2 point reduction with HBOT, 95% CI 0.15 to 4.3, P value 0.04), and the mean Orgogozo Scale score was higher (MD 27.9 points, 95% CI 4.0 to 51.8, P value 0.02).

AUTHORS' CONCLUSIONS:

We found no good evidence to show that HBOT improves clinical outcomes when applied during acute presentation of ischaemic stroke. Although evidence from the 11 RCTs is insufficient to provide clear guidelines for practice, the possibility of clinical benefit has not been excluded. Further research is required to better define the role of HBOT in this condition.

 

J Formos Med Assoc. 2014 Sep;113(9):620-8. doi: 10.1016/j.jfma.2014.03.012. Epub 2014 Apr 29.

Repetitive hyperbaric oxygen therapy provides better effects on brain inflammation and oxidative damage in rats with focal cerebral ischemia

Chen LF1, Tian YF2, Lin CH3, Huang LY4, Niu KC4, Lin MT5.

Author information

  • 1Nursing Department, Cheng Kung University Hospital and Department of Nursing, Chang Jung University, Tainan, Taiwan.

  • 2Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan; Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan. Electronic address: cmh7590@mail.chimei.org.tw.

  • 3Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.

  • 4Department of Hyperbaric Oxygen, Chi Mei Medical Center, Tainan, Taiwan.

  • 5Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan. Electronic address: 891201@mail.chimei.org.tw.

Abstract

BACKGROUND/PURPOSE:

Repetitive hyperbaric oxygen (HBO2) therapy may cause excessive generation of reactive oxygen species. This study assessed whether repetitive or 2-4-day trials of HBO2 therapy (2 treatments daily for 2-4 consecutive days) provides better effects in reducing brain inflammation and oxidative stress caused by middle cerebral artery occlusion (MCAO) in rats than did a 1-day trial of HBO2 therapy (2 treatments for 1 day).

METHODS:

Rats were randomly divided into four groups: sham; MCAO without HBO2 treatment; MCAO treated with 1-day trial of HBO2; and MCAO treated with 2-4-day trials of HBO2. One treatment of HBO2 (100% O2 at 253 kPa) lasted for 1 hour in a hyperbaric chamber.

RESULTS:

Therapy with the 2-4-day trials of HBO2 significantly and dose-dependently attenuated the MCAO-induced cerebral infarction and neurological deficits more than the 1-day trial of HBO2 therapy. The beneficial effects of repetitive HBO2 therapy were associated with: (1) reduced inflammatory status in ischemic brain tissues (evidenced by decreased levels of tumor necrosis factor-α, interleukin-1β, and myeloperoxidase activity); (2) decreased oxidative damage in ischemic brain tissues (evidenced by decreased levels of reactive oxygen and nitrogen species, lipid peroxidation, and enzymatic pro-oxidants, but increased levels of enzymatic antioxidant defenses); and (3) increased production of an anti-inflammatory cytokine, interleukin-10.

CONCLUSION:

The results provide the apparently contradictory finding that heightened oxygen tension reduced oxidative stress (and inflammation), which was reflected by increased antioxidant and decreased oxidant contents under focal cerebral ischemia.

 

Mediators Inflamm. 2013;2013:512978. doi: 10.1155/2013/512978. Epub 2013 Feb 21.

Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke.

Lee YS, Chio CC, Chang CP, Wang LC, Chiang PM, Niu KC, Tsai KJ.

Source

Institute of Clinical Medicine, National Cheng Kung University, Tainan 704, Taiwan.

Abstract

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group.

  • Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

 

Crit Care Nurs Q. 2013 Jul-Sep;36(3):290-8. doi: 10.1097/CNQ.0b013e318294e9e3.

Mechanisms of action of hyperbaric oxygenation in stroke: a review

Sánchez EC.

Source

Hyperbaric Medicine Department, Hospital Agustin O'Horan, SSY, Mérida, Yucatán, Mexico; and Hyperbaric Medicine, School of Medicine, Universidad Nacional, Autónoma de México (UNAM), Mexico City, Mexico.

Abstract

This article outlines the therapeutic mechanisms of hyperbaric oxygenation in acute stroke, based on information obtained from peer-reviewed medical literature. Hyperbaric oxygen is an approved treatment modality for ischemia-reperfusion injury in several conditions. It maintains the viability of the marginal tissue, reduces the mitochondrial dysfunction, metabolic penumbra, and blocks inflammatory cascades observed in acute stroke. Basic and clinical data suggest that hyperbaric oxygen could be a safe and effective treatment option in the management of acute stroke. Further work is needed to clarify its clinical utility when applied within the treatment window of "gold standard" treatments (<3-5 hours).

 

Neurol Res. 2013 Apr 23. [Epub ahead of print]

Hyperglycemia in stroke and possible treatments.

Li WA, Moore-Langston S, Chakraborty T, Rafols JA, Conti AC, Ding Y.

Abstract

Hyperglycemia affects approximately one-third of acute ischemic stroke patients and is associated with poor clinical outcomes. In experimental and clinical stroke studies, hyperglycemia has been shown to be detrimental to the penumbral tissue for several reasons.

  • First, hyperglycemia exacerbates both calcium imbalance and the accumulation of reactive oxygen species (ROS) in neurons, leading to increased apoptosis.

  • Second, hyperglycemia fuels anaerobic energy production, causing lactic acidosis, which further stresses neurons in the penumbral regions.

  • Third, hyperglycemia decreases blood perfusion after ischemic stroke by lowering the availability of nitric oxide (NO), which is a crucial mediator of vasodilation.

  • Lastly, hyperglycemia intensifies the inflammatory response after stroke, causing edema, and hemorrhage through disruption of the blood brain barrier and degradation of white matter, which leads to a worsening of functional outcomes.

 

Many neuroprotective treatments addressing hyperglycemia in stroke have been implemented in the past decade. Early clinical use of insulin provided mixed results due to insufficiently controlled glucose levels and heterogeneity of patient population. Recently, however, the latest Stroke Hyperglycemia Insulin Network Effort trial has addressed the shortcomings of insulin therapy. While glucagon-like protein-1 administration, hyperbaric oxygen preconditioning, and ethanol therapy appear promising, these treatments remain in their infancy and more research is needed to better understand the mechanisms underlying hyperglycemia-induced injuries. Elucidation of these mechanistic pathways could lead to the development of rational treatments that reduce hyperglycemia-associated injuries and improve functional outcomes for ischemic stroke patients.

 

Mediators Inflamm. 2013;2013:512978. doi: 10.1155/2013/512978. Epub 2013 Feb 21.

Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke

Source

Institute of Clinical Medicine, National Cheng Kung University, Tainan 704, Taiwan ; Department of Emergency Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Abstract

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group.

  • Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

 

Inflammation. 2013 Apr 28. [Epub ahead of print]

The Relationship Between N-acetylcysteine, Hyperbaric Oxygen, and Inflammation in a Rat Model of Acetaminophen-induced Nephrotoxicity

Source

Pathology Service, Etimesgut Military Hospital, 06790, Etimesgut, Ankara, Turkey, hcermk@yahoo.com.

Abstract

An overdose of acetaminophen (APAP) produces acute tubular necrosis. The aim of this study was to observe the effects of hyperbaric oxygen (HBO) only and combined with N-acetylcysteine (NAC) on inflammatory cytokines in kidney. Thirty-two male Sprague-Dawley rats were divided into four groups: sham, control (APAP), NAC, and NAC + HBO. In the APAP, NAC, and NAC + HBO groups, renal injury was induced by oral administration of 1 g/kg APAP. The NAC group received NAC (100 mg/kg/day). NAC + HBO group received NAC (100 mg/kg/day) intraperitoneally and HBO underwent at 2.8 ATA pressure with 100 % oxygen inhalation for 90 min every 12 h for 5 days. Rats in the sham group received distilled water only by gastric tube. All animals were killed on 6 days after APAP or distilled water administration. Creatinine, urea, neopterin, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 levels were measured in sera. There was a significant increase in serum creatinine and urea levels in the control group compared to the sham group (in both, p = 0.001). NAC and NAC + HBO significantly decreased serum neopterin, TNF-α, and IL-6 levels compared to control group. APAP administration caused tubular necrosis in the renal. NAC and NAC + HBO treatments significantly reduced APAP-induced renal damage. The results of this study showed that renal dysfunction in APAP toxicity was attenuated by the use of HBO and NAC treatments. The combination of NAC and HBO treatments might be recommended as an effective treatment modality for APAP-induced nephrotoxicity.

 

Brain Res. 2011 Sep 30;1415:103-8. Epub 2011 Aug 6.

Oxygen therapy improves energy metabolism in focal cerebral ischemia

Departments of Neurology, Ruprecht-Karls-University Heidelberg, Germany.

Abstract

Oxygen therapy (OT) with hyperbaric oxygen (HBO) or normobaric hyperoxia (NBO) improves the oxygenation of penumbral tissue in experimental ischemic stroke. However, whether this results in the improvement of energy metabolism is unclear. We investigated the effect of both OTs on tissue acidosis and on ATP production. Beginning 25 min after filament middle cerebral artery occlusion (MCAO), mice breathed either air, 100% O₂ (NBO), or 100% O₂ at 3 ata (HBO) for 60 min. Regional tissue pH was measured using the umbelliferone fluorescence. Regional ATP concentration was depicted by substrate-specific bioluminescence. Severity of ischemia did not differ among groups in laser-Doppler flowmetry. Both NBO (70.1±14.0 mm³) and, more effectively, HBO (57.2±11.9 mm³) significantly reduced volume of tissue acidosis compared to air (89.4±4.0 mm³), p<0.05). Topographically, acidosis was less pronounced in the medial striatum and in the cortical ischemic border areas. This resulted in significantly smaller volumes of ATP depletion (77.8±7.7 mm³ in air, 61.4±15.2 mm³ in NBO and 51.2±14.4 mm³ in HBO; p<0.05). In conclusion, OT significantly improves energy metabolism in the border zones of focal cerebral ischemia which are the areas protected by OT in this model.

 

Hyperbaric oxygen in the treatment of patients with cerebral stroke, brain trauma, and neurologic disease

Life Support Technologies, Inc., and NewTechnologies, Inc., The Mount Vernon Hospital, Westchester Medical Center, New York Medical College, New York, USA.

 

Abstract

  • Hyperbaric oxygen (HBO) therapy has been used to treat patients with numerous disorders, including stroke. This treatment has been shown to decrease cerebral edema, normalize water content in the brain, decrease the severity of brain infarction, and maintain blood-brain barrier integrity.

  • In addition, HBO therapy attenuates motor deficits, decreases the risks of sequelae, and prevents recurrent cerebral circulatory disorders, thereby leading to improved outcomes and survival.

  • Hyperbaric oxygen also accelerates the regression of atherosclerotic lesions, promotes antioxidant defenses, and suppresses the proliferation of macrophages and foam cells in atherosclerotic lesions.

  • Although no medical treatment is available for patients with cerebral palsy, in some studies, HBO therapy has improved the function of damaged cells, attenuated the effects of hypoxia on the neonatal brain, enhanced gross motor function and fine motor control, and alleviated spasticity.

  • In the treatment of patients with migraine, HBO therapy has been shown to reduce intracranial pressure significantly and abort acute attacks of migraine, reduce migraine headache pain, and prevent cluster headache.

  • In studies that investigated the effects of HBO therapy on the damaged brain, the treatment was found to inhibit neuronal death, arrest the progression of radiation-induced neurologic necrosis, improve blood flow in regions affected by chronic neurologic disease as well as aerobic metabolism in brain injury, and accelerate the resolution of clinical symptoms.

  • Hyperbaric oxygen has also been reported to accelerate neurologic recovery after spinal cord injury by ameliorating mitochondrial dysfunction in the motor cortex and spinal cord, arresting the spread of hemorrhage, reversing hypoxia, and reducing edema.

  • HBO has enhanced wound healing in patients with chronic osteomyelitis.

  • The results of HBO therapy in the treatment of patients with stroke, atherosclerosis, cerebral palsy, intracranial pressure, headache, and brain and spinal cord injury are promising and warrant further investigation.