My jaw is on the floor. Finally something!

Front. Hum. Neurosci., 19 October 2017 | Frontiers | Hyperbaric Oxygen Therapy Can Induce Angiogenesis and Regeneration of Nerve Fibers in Traumatic Brain Injury Patients | Frontiers in Human Neuroscience
Hyperbaric Oxygen Therapy Can Induce Angiogenesis and Regeneration of Nerve Fibers in Traumatic Brain Injury Patients

Sigal Tal1,2†, Amir Hadanny1,3,4*†, Efrat Sasson5, Gil Suzin3 and Shai Efrati1,3,6,7*
1Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
2Radiology Department, Assaf Harofeh Medical Center, Zerifin, Israel
3Sagol Center for Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Zerifin, Israel
4Faculty of Medicine, Bar-Ilan University, Ramat Gan, Israel
5WiseImage, Hod Hasharon, Israel
6Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel
7Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel

Background: Recent clinical studies in stroke and traumatic brain injury (TBI) victims suffering chronic neurological injury present evidence that hyperbaric oxygen therapy (HBOT) can induce neuroplasticity.

Objective: To assess the neurotherapeutic effect of HBOT on prolonged post-concussion syndrome (PPCS) due to TBI, using brain microstructure imaging.

Methods: Fifteen patients afflicted with PPCS were treated with 60 daily HBOT sessions. Imaging evaluation was performed using Dynamic Susceptibility Contrast-Enhanced (DSC) and Diffusion Tensor Imaging (DTI) MR sequences. Cognitive evaluation was performed by an objective computerized battery (NeuroTrax).

Results: HBOT was initiated 6 months to 27 years (10.3 ± 3.2 years) from injury. After HBOT, DTI analysis showed significantly increased fractional anisotropy values and decreased mean diffusivity in both white and gray matter structures. In addition, the cerebral blood flow and volume were increased significantly. Clinically, HBOT induced significant improvement in the memory, executive functions, information processing speed and global cognitive scores.

Conclusions: The mechanisms by which HBOT induces brain neuroplasticity can be demonstrated by highly sensitive MRI techniques of DSC and DTI. HBOT can induce cerebral angiogenesis and improve both white and gray microstructures indicating regeneration of nerve fibers. The micro structural changes correlate with the neurocognitive improvements.

Frontiers | Hyperbaric Oxygen Therapy Can Induce Angiogenesis and Regeneration of Nerve Fibers in Traumatic Brain Injury Patients | Frontiers in Human Neuroscience





Some highlights I copied:

In the current study, for the first time in humans, DTI changes of chronic TBI were evaluated before and after HBOT. The increase in FA and decrease in MD post HBOT, together with cognitive function improvement of patients in the late chronic stage of TBI, suggest that brain microstructure recovery can be induced by HBOT.

DTI values, FA and MD, were found in our study to correlate with the improvements in cognitive functions in concordance with previous studies (Sugiyama et al., 2009; Wada et al., 2012; Arenth et al., 2014; Haberg et al., 2015). Memory, executive function and information processing speed were all significantly improved. In correlation with these cognitive improvements, MD decreased in most of the frontal lobe white matter, such as the prefrontal cortex that enables executive control (Miller and Cohen, 2001) and the anterior cingulate gyrus involved in error detection, especially in a Stroop task (Bush et al., 2000). Also, FA increased in most of the long association fibers critical for proper cognitive function:

• SLF–Bi-directional connection of the hemispheric frontal, parietal, temporal and occipital lobes. The SLF plays an important role in high brain functions, particularly language, reflected in information processing speed and executive function tasks (Heilman et al., 1970; Rocha et al., 2005; Sasson et al., 2013). In correlation with those changes, there was a significant improvement in neurocognitive test results in both information processing speed (IPS) and executive functions (EF) (i.e., IPS: 13.1 ± 2.7, p < 0.0001; EF: 11.3 ± 2.7, p < 0.001).

• ILF–Connection between the temporal and occipital lobes on the same hemisphere. The ILF is known to play an important role in visual memory (Bauer and Trobe, 1984; Shinoura et al., 2007). In correlation with those changes, there was a significant improvement in the memory index, which includes a visual memory task (i.e., Memory: 10.5 ± 2.4, p < 0.001).

• Cingulum – A cluster of white matter fibers projecting from the cingulate gyrus in the frontal lobe to the entorhinal cortex in the temporal lobe. The cingulum has been tightly associated with memory disorders (Charlton et al., 2006; Sepulcre et al., 2009). The memory correlates also with the changes in the cingulum.

• Genu of the Corpus Callosum-The largest white matter structure in the brain. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication. Integrity of the corpus callosum is linked to information processing speed and episodic memory (Bucur et al., 2008; Lockhart and DeCarli, 2014). The improvement in information processing speed and memory indices may also correlate with the improvement in the genu of the corpus callosum.

Mechanisms of neuroplasticity and cellular repair by HBOT have been suggested in many animal studies (Hadanny and Efrati, 2016). These include enhanced mitochondrial function and cellular metabolism, improved blood brain barrier and inflammatory reactions, reduced apoptosis, alleviation of oxidative stress, increased levels of neurotrophins and nitric oxide, and up-regulation of axonal guidance agents (Efrati et al., 2013; Efrati and Ben-Jacob, 2014). Moreover, the effects of HBOT on neurons may be mediated indirectly by glial cells. HBOT may also promote neurogenesis of endogenous neural stem cells (Efrati et al., 2013; Efrati and Ben-Jacob, 2014). HBOT may enable the metabolic change simply by supplying the missing oxygen/energy needed for these regeneration processes (Efrati et al., 2013; Efrati and Ben-Jacob, 2014). The ability of HBOT to induce angiogenesis was demonstrated in several different pre-clinical studies (Mu et al., 2011; Lin et al., 2012; Lee et al., 2013; Hu et al., 2014). Hu et al. have demonstrated that HBOT-induced neurogenesis is mediated by ROS/HIF-1α/β-catenin pathway (Hu et al., 2014). In the current study, it is demonstrated that HBOT can induce neuroplasticity in humans even years after the acute insult.

Along with the structural changes, HBOT induces angiogenesis, as shown by the increase of CBF and CBV in this study as well as in our previous study (Tal et al., 2015). The injured areas in the brains post TBI experience hypoxia and hypoperfusion, which serve as a rate-limiting factor for any regenerative process (Graham and Adams, 1971; Graham et al., 1978; Stein et al., 2004; Kim et al., 2010; Ostergaard et al., 2014). HBOT-induced angiogenesis has been amply confirmed in pre-clinical models and can be deduced from brain SPECTs of patients post stroke and post TBI even years after the acute insult (Lin et al., 2012; Boussi-Gross et al., 2013; Efrati et al., 2013; Peng et al., 2014; Duan et al., 2015). The generation of new microvessels renders the local environment non-hypoxic, thus able to induce brain plasticity, enhance neurogenesis and synaptogenesis and foster functional recovery (Chen et al., 2003; Jiang et al., 2005). Unsurprisingly, CBV and CBF increased in the long association fiber tracts discussed above, including corpus callosum, association fibers (SLF, IFOF) and cingulum. Angiogenesis and increased perfusion to the malfunctioning tissue, seen in DSC, serve as infrastructure for the regenerative process and the preservation of newly generated metabolic functioning of the axonal microstructure seen in DTI.

Conclusion

HBOT can induce cerebral angiogenesis and recovery of brain microstructure in patients with chronic cognitive impairments due to TBI months to years after the acute injury. The increased integrity of brain fibers correlates with the functional cognitive improvement. The mechanism by which HBOT can induce brain neuroplasticity can be demonstrated by highly sensitive perfusion MRI and DTI. Further studies, using DTI - MRI, are needed in order to gain better understanding of the neuroplasticity effect of HBOT in a larger cohort of patients with different types of brain injuries.

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It has long been known that vascular improvement was gained from HBOT. This is the first time that cognitive improvement has been noted. The cognitive improvement is slight at only 8 to 13% but it is improvement none the less.

It would be interesting if they showed the test cohort cognitive scales compared to the uninjured population. Did the cognitive improvements lift the subject's function in relation to the general population? My memory and processing speed scales in the bottom 10% of the population. Would it be improved to the bottom 11-12% of the population? Would somebody whose functions were at the 50% level be improved to the 56% level. There is a lot of information missing. Improvement based on population scales relates to ability to function in society.

These improvements were with 60 dives. It is probable that additional dives would bring additional benefit. Correct me if I'm wrong but this is also the first time that DTI changes have been linked to cognitive improvements.

Also, here is an example of what you're looking for. The testing results are at the end of the video. This was with 40 dives for this man. I'd also have to say the look on his face alone before and after says it all. This man is CLEARLY leading a more normal life.

Navy/Army Veteran before and After HBOT - YouTube

Also this thread:

My Hyperbaric Oxygen Therapy Experience (HBOT)

So there's two examples.

The YouTube chart is without explanation and is hard to understand. HealtheWarriors.org is defunct so the supporting information is not available. From the second thread and chart, I see they used CNS Vital Signs as a Computerized NeuroCog Test. It appears to be the one the Army/Navy vet used. They were one of the first, even before ImPACT. teaaquinns results were substantially better that the Israeli study and the other studies I have seen.

Prior studies showed there is a maximum benefit in the 40 to 80 dives range. Once full vascularization is achieved, there would not be a need to continue.

Both teaaquinn and the Army/Navy vet fit with the prior research that indicated those with the worst functions saw the most improvement. I took the CNS Vital Signs battery 15 years ago. Maybe it is in my archives.

If the Israeli study was more comprehensive, it would correlate the injury severity with the results.

It would be great if Dr Harch would publish his results. His early research suggests 1.25 to 1.5 atmospheres is optimal.

As the question has been for a decade, how do we get insurance to pay for or contribute to HBOT? How do we get the wound care HBOT centers to offer it for mTBI since it is still off-label?

So further dives would not improve white matter integrity or other symptoms further? How do we know that? The possible mechanisms of action listed are extensive:

I also don't see how it is hard to understand the military guy's test results. It is almost the exact same chart as tea's.

Once I finally figured out the color coding and relationship between the right columns and the left columns, it made sense. I have read many NeuroPsych Assessment reports and the CNS Vital Signs report requires a lot more effort and assumptions to understand.

The research points to the vascularization as the root cause of the improvements. The vascularization has been understood for decades. By vascularization, they mean growth of new capillaries. If there is a limit to increased capillary growth, it would suggest the grey and white matter would have the same limit.

Some studies suggest that the capillaries are part of the damage along with diffuse axonal injury.

If I remember correctly, the studies that used CNS Vital Signs were started in a VA hospital in Florida. Bay Pines I think. The study from a decade ago or so showed a minority of subjects experienced improvements. They could not understand why increased capillaries did not result in other improvements.

"It would be great if Dr Harch would publish his results."

As far as I can see from PubMed Dr Harch has published 14 papers over the period 1994-2017 (search string "Harch PG").

The most recent one (2017) is a case report of a young child who was treated with HBOT after a drowning event (Subacute normobaric oxygen and hyperbaric oxygen therapy in drowning, reversal of brain volume loss: a case report. - PubMed - NCBI).

The next most recent one (2015) seems to me to be largely polemical in nature (Hyperbaric oxygen in chronic traumatic brain injury: oxygen, pressure, and gene therapy. - PubMed - NCBI).

Was 1.3-1.5 atmospheres used? Dr. Harch has stated that higher pressures are less effective for TBI.

kiwi, Dr Harch has not published results of the study he started a few years ago. I check his web site from time to time with hopes that he has something good to report. He has written plenty of anecdotal reports. He likes to write about that near drowning event.

The studies used 1.5 atmospheres if I recall correctly. There are plenty of studies that show 1.25 to 1.5 as adequate for benefit. It does not take much to increase oxygen perfusion. I tried searching for the Florida study. It might have been in Virginia, instead. Bay Pines did a different concussion study.

Here is another set of before and after cognitive tests from some guy who was in a car accident.

Drum roll please……………… | our headbangers ball

** edit**

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