Experimental Models For Hbot
Although HBOT is available and used worldwide in human medicine, many scientific discoveries that report its beneficial effects for human diseases were first investigated in animal models, primarily rodents and rabbits but also dogs, cats, and pigs . Current protocols for murine HBOT administration include use of specifically designed homemade devices and commercially available hyperbaric chambers such as the p-1100 from Barotec Hanyuda . To mimic hyperbaric therapy that is administered to humans, mice breathe pure oxygen at pressures ranging from 2 to 4 ATA for 6090 min daily for at least a week. A minimum of 15 min of pressurization and depressurization is often allowed for animals to adjust to the changes in pressure. Animal models have demonstrated that HBOT creates the necessary oxygen gradients between the hyperoxygenated blood and injured tissues promoting several beneficial effects in multiple pathologies. As the relationship between cerebral microvascular health and cognitive function has become well-recognized , great scientific interest is devoted to understanding the potential therapeutic effects HBOT specifically exerts on the brain and its microvasculature.
Study Indicates Efficacy Of Hyperbaric Oxygen Therapy In Reversing Alzheimers Activators
A new study, published in the peer-reviewed medical journal Aging, marks the first time non-pharmaceutical clinical exploration has proved efficacious in reversing the main activators of Alzheimers disease. Using a specific protocol of hyperbaric oxygen therapy , cerebral blood flow was increased in elderly patients by 1623%, alleviating vascular dysfunction and amyloid burden.
The studypart of a comprehensive research programme directed towards ageing and accompanying ailments as a reversible diseaseholds promise for a new strategic approach in the prevention of Alzheimers by not only targeting its biomarkers or symptoms, but also by addressing the core pathology and biology responsible for advancement of the disease. This is according to a press release from Aviv Clinicswhich focuses on the research and treatment of age-related cognitive and functional decline, and novel applications of HBOT in this space.
This comprehensive research, the release adds, was conducted at the Sagol School of Neuroscience at Tel Aviv University in Tel Aviv, Israel, and the Sagol Center for Hyperbaric Medicine and Research at Shamir Medical Center in Beer Yaakov, Israel. It was led by study co-authors Shai Efrati, Uri Ashery, Ronit Shapira, Pablo Blinder and Amir Hadanny.
Hbot Reduces The Amyloid Load Of 5xfad Mice By Reducing The Number Of Newly
We first asked if increasing oxygen delivery to the brain by administrating HBOT reduced amyloid burden. To that end, we employed a custom-made HBO chamber to expose 6 month-old 5XFAD and wild type mice to HBOT at 2 ATA for 60 minutes per day, 5 days a week for 4 weeks . To assess the effect of HBOT on amyloid burden in the treated 5XFAD mice, brains were stained with anti-A pan-antibodies . We found significant reduction in amyloid burden in the hippocampus of HBO-treated 5XFAD mice, as manifested by the reduced percentage of hippocampal area displaying 4G8 immunoreactivity , decreased numbers of plaques and smaller plaque size , relative to control 5XFAD mice exposed to normobaric conditions.
We then analyzed the levels of soluble and insoluble levels of A42 and A40 in the hippocampus by ELISA . Following 1 month of HBOT, levels of insoluble A42 were reduced by ~56% , while A40 levels were reduced by ~45% in HBO-treated 5XFAD mice compared with control 5XFAD mice. In contrast, soluble A42 and A40 levels were unchanged . Collectively, these data demonstrate that HBOT reduced the amyloid load in the hippocampal formation of 5XFAD mice.
Taken together, these results suggest that HBOT both attenuates the appearance of newly- formed plaques and causes a reduction in the volume of pre-existing plaques.
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Mechanistic Explanation For The Effects Of Hbot On Cognition
A series of studies using animal models for brain injuries and brain diseases showed an improvement in the animals’ cognitive performance and provided a mechanistic understanding of some of HBOTs effects. Not surprisingly, these effects are not mediated by a single pathway, but were found to be mediated by several pathways, including inhibition of apoptosis, improvement of mitochondrial function, stem cell proliferation, enhancement of antioxidant defense activity, reduction in neuroinflammation, and neuroprotection.
Mitochondria consume roughly 85 to 90% of the oxygen that we breathe and are the major source of ATP production. It is therefore likely that the main molecular target of HBOT is the mitochondrion. Humanin, a neuroprotective mitochondrion-derived peptide, was shown to be elevated in VD patients following HBOT , suggesting a major role for mitochondrial activity in HBOT’s mechanisms of action. Recent studies have suggested facilitation of mitochondrial transfer from astrocytes to neuronal cells, making the latter more resilient to neuroinflammation . In a rat model for AD, HBOT reduced mitochondria-mediated apoptosis signaling by increasing Bcl-2, which is anti-apoptotic, and decreasing Bcl-2-associated X protein , which is pro-apoptotic .
Neurologylive: Could You Walk Through What Prompted This Work How Did We Get To This Point With Hyperbaric Oxygen Therapy
Shai Efrati, MD: Actually, it all started something like 15 years ago. I started a small study and the goal was to prove that neurons cannot be regenerated. That’s was the goal, and I got the opposite results. Since then, things are moving in a completely different direction.
We are working on regenerating brain tissue. The main issue is to refer to the brain as a tissue. The injury that we have in the brain is just like any other injuries we have in other parts of the body. They have common dominant pathophysiology, whether you want to heal a peripheral wound that you have in the leg, or whether you want to heal a wound that is in your brain. The main difference between the one that we have in the leg and the one in the brain is that the wound in the leg is something that you can see. It’s tangible. You can smell it, you can see it, you understand what is happening. With the brain, it’s high tech. We are looking at it through CT or MRI. We’re speaking about the brain in a mystic fashion, about cognitive personality. But, surprise, surpriseit’s a tissue.
If we cannot take the stem cells out and inject them, let’s stimulate our own body to generate stem cells. Amazing idea. The main trigger for stem cell proliferation, is hypoxiaa lack of oxygen. So, if we want the human being to stimulate the stem cells, we can take a person, hold his breath and stop his heartbeat, and then you will have stem cells. There is only one problem. It’s not healthy.
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Integrative Role Of Hyperbaric Oxygen Therapy On Healthspan Age
- 1Vascular Cognitive Impairment and Neurodegeneration Program, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- 2International Training Program in Geroscience, Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network , Szeged, Hungary
- 3International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
- 4Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
Hyperbaric Oxygen Therapy For Alzheimer’s Prevention
Megan Brooks
Hyperbaric oxygen therapy increases cerebral blood flow and improves cognitive performance in older adults with memory problems, early research suggests.
“By treating vascular dysfunction, we’re mapping out the path toward Alzheimer’s prevention,” study investigator Shai Efrati, MD, with the Sagol School of Neuroscience, Tel Aviv University, Israel, said in a statement.
“More research is underway to further demonstrate how HBOT can improve cognitive function and become an influential tool in the imperative fight against the disease,” said Efrati, who heads the Sagol Center for Hyperbaric Medicine and Research in Israel.
The study was September 9 in the journal Aging.
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Hbot Reduces Hypoxia And Hypoxia Inducible Factor
We next investigated whether the changes in CBF following HBOT reduced hypoxia in the hippocampal area of 5XFAD mice. Fourteen days following the last session of HBO or control treatment, mice were injected with Hypoxyprobe, a label which is only activated and detectable in hypoxic cells, characterized by a partial pressure of oxygen below 10mm Hg . As can be seen in Figure 6, the 5XFAD control mice showed increased reactivity of Hypoxyprobe in hippocampal areas CA3 and CA1 , as compared with the same areas in their wt counterparts. Remarkably, HBOT significantly reduced the reactivity of Hypoxyprobe in the hippocampal formation of 5XFAD mice in both CA3 and CA1 , relative to 5XFAD control mice.
Testing Of Serum Humanin Levels
All subjects were examined after overnight fasting for at least 8 h before and aftertreatment in both groups. Serum Humanin levels were detected before the treatment and onthe second day after 12 weeks of treatment. A total of 5 ml of blood was drawn into anEDTA-containing tube and was centrifuged for 15 min at 3000 g. The serumwas obtained and stored at 80°C for analysis. Humanin concentrations were measured by acommercial ELISA reagent kit in strict accordance with the instructions, and was completed by the Central Laboratory ofTaian City Central Hospital.
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Studies On Hyperbaric Oxygen Therapy And Dementia
This particular report examined eight different databases, China Science and Technology Journal Database , and WanFang) and 25 randomized controlled clinical trials involving 1,954 patients.
This meta analysis aimed to determine the effectiveness of hyperbaric oxygen therapy in patients with vascular dementia. Throughout the courses of these studies, there were groups that solely had medication, groups that only did hyperbaric oxygen therapy, and groups that had treatment of both.
There was much more improvement seen in the hyperbaric groups both with medication and without. They saw what shows strikingly improved mini mental state examinations and massive improvements in activities of daily living.
The curative administration of 100% oxygen in the pressurized hyperbaric chamber at an atmosphere of more than 1.4 has shown therapeutic effects in treating vascular dementia.
The researchers believe these results are due to the increase of oxygen supply, decrease of intracranial pressure, the relief of brain edema, promotes tissue healing and angiogenesis , improvement of metabolism, lessening oxidative stress, improving mitochondrial function, improving cell differentiation, and more.
Though still not fully understood, researchers claim that the efficacy and safety of hyperbaric oxygen therapy for dementia is undisputable.
Improve dementia with hyperbaric oxygen therapy
Summary
Understanding The Types Of Dementia:
We call the process of knowing and perceiving cognition. When people get dementia or related disorders like Alzheimers disease, they experience a cognitive weakness and decline that impacts their daily living.
Over 50 different medical conditions produce symptoms of dementia, and the nature of these symptoms can vary. Early symptoms can be subtle. Thats why Dr. Spiegel takes such a comprehensive approach to diagnosing his patients. Knowing precisely which type of dementia you or your loved one may be suffering from enables him to prescribe the best possible course of care.
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Study On Animals Genetically Engineered To Develop Alzheimer And A Group Of Subjects Over 65 With Memory Decline Showed Improved Vascular Function
A research team in Israel has succeeded in reversing brain trauma using hyperbaric oxygen therapy . This is the first time in the scientific world that non-drug therapy has been proven effective in preventing the core biological processes responsible for the development of Alzheimers disease.
HBOT involves having patients sit in a special chamber where the atmospheric pressure is much higher than normal, breathing air composed of 100 percent oxygen. This form of therapy is considered safe for treating many medical conditions, and can induce the repair of damaged brain tissue and renewed growth of blood vessels and nerve cells in the brain.
A specific HBOT protocol devised by Tel Aviv University and Shamir Medical Center researchers Prof. Shai Efrati, Prof. Uri Ashery, Dr. Ronit Shapira, Dr. Pablo Blinder and Dr. Amir Hadanny resulted in cerebral blood flow improving in elderly patients by 16-23%, alleviating vascular dysfunction, reducing the volume of pre-existing amyloid plaques and slowing the formation of new ones. These protein plaques are linked to severe degenerative conditions such as Alzheimers.
Their findings were published in the journal Aging.
The study, part of a comprehensive research program that looks at aging and accompanying ailments as a reversible disease, could lead to a new strategic approach to preventing Alzheimers.
Could Hyperbaric Oxygen Therapy Improve Cognitive Function In Dementia
The director of the Sagol Center for Hyperbaric Medicine and Research at Yitzhak Shamir Medical Center offers insight into the attempt to regenerate injured tissue in the brain as a way to potentially treat Alzheimer disease and dementia.
Shai Efrati, MD
This is the first of a 2-part interview. For Part 2, .
Hyperbaric oxygen therapy, which has been approved by the FDA for many different indications, was only recently studied for cognitive challenges, with data suggesting that it may offer new hope for cognitive decline.
It has previously shown statistically significant improvements in all memory measures and indicate that it can lead to significant neurological improvements in post-stroke patients even at chronic late stages.1,2 Now, new data have implied that it may hold promise for those with diseases like Alzheimer and dementia. A randomized controlled clinical trial of 63 healthy older adults compard placebo to hyperbaric oxygen therapy for 3 months, showing that the oxygen therapy appeared to induce cognitive enhancements via mechanisms involving regional changes in cerebral blood flow, as evaluated by perfusion magnetic resonance imaging . A significant group-by-time interaction in global cognitive function was observed compared to control , with the most impressive improvements in attention and information processing speed .3
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Study Inclusion And Characteristics
Of the 549 potentially relevant studies searched from the eight databases, 341 duplicated publications were removed, and 208 papers were left for further screening. After reading titles and abstracts, there were 113 reports left, and 87 articles were excluded for one of following reasons: irrelevant study, not a randomized controlled trial, conference papers. Finally, the remaining 25 RCTs with a total of 1.954 patients meeting our inclusion criteria were included in the final review . Additionally, all trials were performed and published in China. Among the 25 studies, five comparisons were employed between the HBOT group and the control group, including HBOT+CT+ oxiracetam vs. CT+ oxiracetam , HBOT+CT+ butylphthalide vs. CT+ butylphthalide , HBOT+ CT+ donepezil vs. CT+ donepezil , HBOT+ CT+ nicergoline vs. CT +nicergoline , and HBOT+CT vs. CT . The treatment duration lasted from 3 to 16 weeks, and sample sizes varied from 40 to 156. Twelve studies reported specific adverse events .
Figure 1. The flowchart of study selection.
Table 1. The baseline characteristics of the 25 studies.
In Another Study Published In 2020
Researchers found that one course of hyperbaric oxygen treatment significantly improved the cognitive function in AD patients and also ameliorated the reduced brain glucose metabolism found in some patients. The writers suggested that hyperbaric oxygen is beneficial in reducing the hypoxia which could be a potential contributor to the pathogenesis of AD. Therapeutics like hyperbaric oxygen treatment improve tissue oxygen supply and ameliorates hypoxic conditions in the brain, which is key in alleviating the symptoms seen in Alzheimers and dementia.
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Foundation Offers Free Online Memory Screenings
The improvements in these scores correlate with improved short and working memory, and reduced times of calculation and response, as well as increased capacity to choose and concentrate on a relevant stimulus, the researchers wrote.
The team said this is the first time that a non-drug therapy has been proven effective in preventing the core biological processes responsible for the development of Alzheimers disease.
Use of HBOT may be a new strategic approach for preventing Alzheimers, they said.
By treating the root problem that causes cognitive deterioration with age, we are in fact mapping out the way to prevention, said Shai Efrati, MD, a study co-author and an associate professor at both the Sackler School of Medicine and the Sagol School of Neuroscience at Tel Aviv University.
It is likely that hyperbaric medicine can potentially provide the opportunity for living with good brain function without relating to chronological age, Efrati said.
The idea is to commence therapy before the onset of clinical symptoms of Dementia and before deterioration and loss of extensive brain tissue. This is the stage at which blood vessels become occluded, and the blood flow and the oxygen supply to the brain are diminished a phenomenon that can already take place at a relatively early age, he added.
Hbot Improves The Performance Of 5xfad Mice In Behavioral Tasks
Finally, we explored if the mitigating effects of HBO treatment on AD pathology are associated with an improvement in the performance of 5XFAD mice in behavioral tasks. We found that HBO-treated 5XFAD mice showed improved nest construction abilities, given how they built nests with higher walls and attained higher nest scores . Moreover, the treated mice showed improved exploratory behavior, as compared to control 5XFAD mice .
Spatial recognition memory was investigated by testing the natural preference of mice for exploring novel over familiar spatial contexts in a Y-maze test . Control 5XFAD mice showed a decreased time index in this assay, as compared to their wt littermates , HBOT significantly reversed this trend . We then tested the effect of HBOT on hippocampus-dependent contextual memory by performing trace fear conditioning . Control 5XFAD mice showed impaired contextual memory, relative to their wt littermates, as reflected by lower freezing activity in the training chamber 24 h following conditioning . Interestingly, this impairment was recovered in HBO-treated 5XFAD mice .
Taken together, these results suggest that HBOT ameliorated the performances of 5XFAD mice in memory and behavioral tasks.
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