HBOT after Blast Brain Injury, Study

Hyperbaric Oxygen Treatment after the Blast Injury of Rabbitbrain the Expression of AQP4 and PWI in the Study Phase

Hyperbaric Oxygen Treatment after the Blast Injury of Rabbit brain the Expression of AQP4 and PWI in the Study Phase

23. June 2012 · Comments Off · Categories: Surgery · Tags: aquaporin-4, brain injury, hyperbaric oxygen treatment, magnetic resonance perfusion imaging, Rabbit

Title

Hyperbaric Oxygen Treatment after the Blast Injury of Rabbit brain the Expression of AQP4 and PWI in the Study Phase

Abstract

Objective:To establish explosive brain injury model in rabbits;To investigate the expression of aquaporin 4(AQP4) in model of explosive brain of rabbits injury,and perfusion changes in the expression, to explore the formation of brain edema after blast injury mechanism, and early hyperbaric oxygen treatment of traumatic brain edema formation and development of the role of early treatment for clinical hyperbaric oxygen provide the basis for traumatic brain edema.Method:①30 New Zealand white rabbits, weighing 2.0 ~ 2.5kg, in accordance with the vertical distance between the detonators and the skull group, were randomly divided into groups 5.0cm, 6.5cm group, 8.0cm group, n = 10. 600mg TNT equivalent of paper detonators were used to explode respectively 5.0cm, 6.5cm, and 8.0cm vertical distance from the top of the rabbit head, observing animal survival after injury, and using magnetic resonance imaging methods to understand the pathology and brain damage in each group.②150 New Zealand rabbits were randomly divided into non-treatment group, treatment group and control group, and 10 rabbits were in the latter. Explosive brain injury model was made by paper detonator. Injuryed rabbits were randomly divided into 1h、6h、12h、24h、72h、7d、14d ,14 groups according to a further killed time points after injury, and each group has 10 rabbits. Using dry weight to measure the content water in brain tissue, and using RT-PCR method and image analysis to detect the group at different time points aquaporin 4 (AQP4)mRNA expression, and Western blotting to measure the expression of AQP-4 in brain tissue. Using magnetic resonance perfusion imaging ( PWI) injury time points detected in brain tissue blood perfusion. Finally, it was used for statistical analysis.Results:①5 rabbits died immediately after injury and 4 rabbits died within 3 days in group 5.0cm,and only one survived more than 7 days;The rabbit has appeared most extensive brain contusion, cortical surface vessel rupture occurs, and significant fragmentation in brain tissue, large subdural hematoma, and significant brain stem contusion. All rabbits in group 6.5cm survived more than 7 days,except that 1 rabbit died on the 4th day after injury because of inability eating. 4 rabbits occurred epilepsy and got paralysis of limbs; Pathology observed in the survival of the rabbits had cerebral cortex partial rupture of blood vessels, brain edema and obvious laceration and contusion lesions clear boundary with the surrounding brain tissue. All rabbits in group 8.0cm survived, but showed no significant changes in the brain.②Blast injury after contusion brain 1h aquaporin 4 (AQP4) mRNA expression increased, and in turn increased, 72h peak (P <0.05), 7d pm down. Brain tissue aquaporin 4 (AQP4) began to express 1h after injury increases, and 72h reached its peak (P <0.05), it turned to down after 7d, but it still maintained on a high level. Brain tissue water content and water aquaporin 4 (AQP4) expression were the same. The correlation analysis, aquaporin 4 (AQP4) expression and brain tissue water content was positively correlated (r=0.8767,P<0.001). The hyperbaric oxygen treatment, aquaporin 4 (AQP4) expression at different time points are different degrees of decline, aquaporin 4 (AQP4) expression of injury group compared with control group at after 6h points were lower (P <0.05 ). Blast injury after contusion brain 1h AQP4 mRNA expression increased, and in turn increased, 72h peak (P <0.05), 7d pm down, but still maintain a high level. After intervention by hyperbaric oxygen, in 6h, AQP4 mRNA expression was significantly lower than the injury to 14d is still significantly lower (P <0.05). Post-traumatic cerebral contusion early peripheral blood perfusion decreased significantly to 6 hours after injury, blood perfusion decreased to the lowest (P <0.05), then gradually increased, and maintain a perfusion (close to the control group) for 2 weeks. The hyperbaric oxygen treatment group than in the early trauma group (1-6 hours after injury) perfusion decreased more significantly. 12 hours after infusion began to rise, and non-treatment group was essentially flat.Conclusion:①Detonators and the vertical distance of the skull 6.5cm, can produce good stability, repeatability strong blast injury model of rabbit brain.②The expression of post-traumatic brain aquaporin 4 (AQP4) in traumatic brain is closely related to the formation and development of injury and brain edema. Aquaporin 4 (AQP4) expression may be associated with brain ischemia and hypoxia in the Hyperbaric oxygen intervention aquaporin 4 (AQP4) expression was significantly reduced. Instead, the blood perfusion than the control group and non-treatment group decreased significantly, suggesting that brain tissue oxygen levels of early trauma and aquaporin 4 (AQP4) expression is closely related to early hyperbaric oxygen therapy on the relief plays an important role in traumatic brain edema. Early hyperbaric oxygen therapy can improve cerebral blood oxygen contusion, increased blood oxygen content, ease the secondary cerebral hypoxia caused by cerebral edema.

STUDY: Hyperbaric Oxygen Therapy helped prevent or slow the progression of type 1 diabetes in mice

By Serena Gordon
HealthDay Reporter
FRIDAY, May 11 (HealthDay News) -- Treatment with hyperbaric oxygen therapy helped prevent or slow the progression of type 1 diabetes in mice, according to new research. It is too early to say if the results might apply to humans, however.
In mice, the treatment caused changes in the immune system's response to newly developing diabetes, and reduced the risk of diabetes between 20 and 40 percent. In the mice that still developed diabetes, the hyperbaric therapy delayed disease progression, the investigators found.
"Hyperbaric oxygen therapy is a relatively non-harmful way of enhancing oxygen delivery to the tissues," said the study's senior author, Dr. Antonello Pileggi, director of the preclinical cell processing and translational models program at the Diabetes Research Institute of the University of Miami Miller School of Medicine.
"We were able to suppress the transfer of the disease (in mice) before the onset of the disease. After diabetes had occurred, the efficacy [of hyperbaric therapy] was much less," said Pileggi. He said that combining hyperbaric therapy with medications might enhance the effectiveness of both treatments.
Results of this study, released online May 7, will be published in the July print issue of Diabetes.
In type 1 diabetes, the immune system mistakenly attacks healthy cells in the pancreas called beta cells. Beta cells produce the hormone insulin that allows your body to metabolize carbohydrates from food, providing fuel for energy. People with type 1 diabetes must replace the lost insulin through multiple daily injections or a pump.
Hyperbaric oxygen therapy -- commonly used to treat scuba divers who develop "the bends" from rising to the surface too quickly -- is delivered in a special pressurized chamber. The pressure inside the chamber is about two and half times greater than the normal pressure in the atmosphere, according to the U.S. National Library of Medicine. This puts more oxygen in your blood. Hyperbaric therapy can also be used to treat bone infections, burns, carbon monoxide poisoning, and wounds that aren't healing well, such as ulcers in people with diabetes. Currently, not very many hospitals offer hyperbaric oxygen therapy.
For the current research, Pileggi and his colleagues used two types of mice. One type develops diabetes spontaneously. It's not exactly the same as type 1 diabetes in humans, but it is very similar, and Pileggi said "it's a good surrogate of type 1." And, the second type doesn't develop diabetes on its own, but the researchers induced diabetes.
In the mice that spontaneously develop diabetes that received hyperbaric therapy, the risk of developing diabetes was reduced by 20 percent. In the mice with induced diabetes, the treatment reduced the risk of diabetes by 40 percent, according to the study. In the mice that still developed diabetes in both groups, treatment with hyperbaric therapy helped delay the onset or progression of the disease.
Pileggi said that the researchers aren't yet clear exactly how hyperbaric therapy prevents or slows the disease, but it's clear the therapy has positive effects on the immune system.
The researchers were also pleasantly surprised to see that the therapy caused a significant increase in creation of new beta cells. "If you can reeducate immune cells and enhance the beta cell mass, that's an ideal situation. But, it's not a silver bullet for diabetes. It could be an adjuvant to other therapies," said Pileggi.
Pileggi said the researchers will test combination treatments but added that it's too soon to guess when such a treatment might be tried in humans.
Another expert said any application to humans is years away.
"This is a novel idea from a good research group. But, while the mouse model is good to study, it doesn't mean that what is affected in mice will be affected in men," said Dr. Joel Zonszein, director of the clinical diabetes center at Montefiore Medical Center in New York City.
Also, it would be difficult to choose who would receive such a therapy, he said, because there isn't a reliable test to determine who will develop type 1 diabetes. There are tests for the antibodies present in type 1, but some people who never develop diabetes have those same antibodies.

Hyperbaric oxygen therapy improves spatial learning and memory

Brain Res. 2007 Oct 12;1174:120-9. Epub 2007 Aug 16. Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury. Harch PG, Kriedt C, Van Meter KW, Sutherland RJ. Source Department of Medicine, LSU Health Sciences Center in New Orleans, Harvey, Louisiana 70058, USA. paulharchmd@aol.com
ABSTRACT:
In the present experiment we use a rat model of traumatic brain injury to evaluate the ability of low-pressure hyperbaric oxygen therapy (HBOT) to improve behavioral and neurobiological outcomes. The study employed an adaptation of the focal cortical contusion model. 64 Male Long-Evans rats received unilateral cortical contusion and were tested in the Morris Water Task (MWT) 31-33 days post injury. Rats were divided into three groups: an untreated control group (N=22), an HBOT treatment group (N=19) and a sham-treated normobaric air group (N=23).

The HBOT group received 80 bid, 7 days/week 1.5 ATA/90-min HBOTs and the sham-treated normobaric air group the identical schedule of air treatments using a sham hyperbaric pressurization. All rats were subsequently retested in the MWT. After testing all rats were euthanized. Blood vessel density was measured bilaterally in hippocampus using a diaminobenzadine stain and was correlated with MWT performance. HBOT caused an increase in vascular density in the injured hippocampus (p<0.001) and an associated improvement in spatial learning (p<0.001) compared to the control groups. The increased vascular density and improved MWT in the HBOT group were highly correlated (p<0.001).

In conclusion, a 40-day series of 80 low-pressure HBOTs caused an increase in contused hippocampus vascular density and an associated improvement in cognitive function. These findings reaffirm the clinical experience of HBOT-treated patients with chronic traumatic brain injury.
PMID: 17869230

New Study on Brain Injury

New Study on Brain Injury!

http://www.liebertonline.com/doi/pdfplus/10.1089/neu.2011.1895

Brain injury study under way at Camp Pendleton

MILITARY: Brain injury study under way at Camp Pendleton
MILITARY: Brain injury study under way at Camp Pendleton
http://www.nctimes.com/search/?l=50&sd=desc&s=start_time&f=html&byline=By%20MARK%20WALKERmlwalker%40nctimes.comNorth County Times Posted: Friday, September 30, 2011 8:00 pm



A hyperbaric chamber at Camp Pendleton is being used to treat troops with mild traumatic brain injuries in a trial program to see if it speeds their recovery. Courtesy photo
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Related: MILITARY: Brain-injured Marines to test new treatment
A half-dozen Marines with brain injuries from combat in Afghanistan or Iraq will crawl inside a hyperbaric chamber at Camp Pendleton next week to begin eight weeks of treatment breathing pure oxygen to see if it speeds their recovery.
Up to 100 base troops eventually are expected to take part in the study trying to find the best treatments for what is known as traumatic brain injury.
Many other troops suffering from post-traumatic stress disorder from their battlefield experiences also are expected to take part in the study to see if it helps them heal.
"I'm really hopeful that this potential treatment will help," said Navy Cmdr. James Caviness, head of occupational health services and the study's principal investigator at Naval Hospital Camp Pendleton.
"The anecdotal reports of hyperbaric chamber use in civilian settings are positive, and we need to rigorously look at this to see if we can use it," he added.
The troops taking part in the study are volunteers. Hundreds of others at the Marine Corps' Camp Lejeune in North Carolina and at Army bases at Fort Carson, Colo., and Fort Gordon, Ga., are taking part in similar studies.
Researchers will measure whether the use of the chamber can ease the headaches, memory loss and other ailments from mild traumatic brain injury, which are common after-effects for troops who are injured in roadside bomb attacks.
When the program was designed last year, U.S. Army Col. Richard Ricciardi at the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury described it as one of many commissioned by the Pentagon to improve brain injury care.
"It's one part of the arsenal of treatments being tested across the system to tackle this challenging problem and do the right thing for our warriors," he said.
Traumatic brain injury has emerged as a common injury among troops in Iraq and Afghanistan, where anti-government forces rely on homemade bombs as a primary weapon.
More than 134,000 U.S. troops have been treated for such injuries since the Afghanistan and Iraq wars began, according to Pentagon statistics.
Close to 1,400 service members have suffered concussions or traumatic brain injury so far this year, according to the Defense Department.
The malady is divided into three classifications. Mild cases involve loss of consciousness for up to 30 minutes and mild amnesia.
The hyperbaric chamber at Camp Pendleton is inside a trailer adjacent to the hospital. Pressure inside it will be equivalent to what divers experience at about 20 feet under water.
The pressurization forces pure oxygen into the cells. The experiment tests whether the repeated trips to the chamber speed healing.
Some troops breathe pure oxygen administered under a tentlike hood so no gas escapes. Others will get a lesser amount of pure oxygen, and a third group will breathe normal air under near-similar pressure conditions to test the results.
Camp Pendleton's role is to help establish the precise treatment regimen and baseline testing troops will undergo to see if the treatment helps.
"There are a lot of unknowns about traumatic brain injury, which has emerged as the 'signature injury' of the wars in Iraq and Afghanistan," Caviness said. "We need to learn a lot more, and this study will hopefully demonstrate it is something we can use."
Troops suffering from moderate or severe brain injuries are not part of the study because there is no evidence hyperbaric chambers speed their recovery.
Among the measurements technicians will use are batteries of memory, mood and motor function tests administered to troops before the study, as it takes place and at the end of the eight weeks.
Read more: http://www.nctimes.com/news/local/military/article_b93bb889-8830-5f98-801b-0d5278c1871b.html#ixzz1ZebPDmYw

Autism changes molecular structure of the brain, UCLA study finds

Discovery points to a common cause for multifaceted disease By Elaine Schmidt May 25, 2011

For decades, autism researchers have faced a baffling riddle: how to unravel a disorder that leaves no known physical trace as it develops in the brain.

Now a UCLA study is the first to reveal how the disorder makes its mark at the molecular level, resulting in an autistic brain that differs dramatically in structure from a healthy one. Published May 25 in the advance online edition of Nature, the findings provide new insight into how genes and proteins go awry in autism to alter the mind.

The discovery also identifies a new line of attack for researchers, who currently face a vast array of potential fronts for tackling the neurological disease and identifying its diverse causes.

"If you randomly pick 20 people with autism, the cause of each person's disease will be unique," said principal investigator Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics and a professor of neurology and psychiatry at the David Geffen School of Medicine at UCLA. "Yet when we examined how genes and proteins interact in autistic people's brains, we saw well-defined shared patterns. This common thread could hold the key to pinpointing the disorder's origins."

The research team, led by Geschwind, included scientists from the University of Toronto and King's College London. They compared brain tissue samples obtained after death from 19 autism patients and 17 healthy volunteers. After profiling three brain areas previously linked to autism, the group zeroed in on the cerebral cortex, the most evolved part of the human brain.

The researchers focused on gene expression — how a gene's DNA sequence is copied into RNA, which directs the synthesis of cellular molecules called proteins. Each protein is assigned a specific task by the gene to perform in the cell.

By measuring gene-expression levels in the cerebral cortex, the team uncovered consistent differences in how genes in autistic and healthy brains encode information.

"We were surprised to see similar gene expression patterns in most of the autistic brains we studied," said first author Irina Voineagu, a UCLA postdoctoral fellow in neurology. "From a molecular perspective, half of these brains shared a common genetic signature. Given autism's numerous causes, this was an unexpected and exciting finding."

The researchers' next step was to identify the common patterns. To do this, they looked at the cerebral cortex's frontal lobe, which plays a role in judgment, creativity, emotions and speech, and at its temporal lobes, which regulate hearing, language and the processing and interpreting of sounds.

When the scientists compared the frontal and temporal lobes in the healthy brains, they saw that more than 500 genes were expressed at different levels in the two regions.

In the autistic brains, these differences were virtually non-existent.

"In a healthy brain, hundreds of genes behave differently from region to region, and the frontal and temporal lobes are easy to tell apart," Geschwind said. "We didn't see this in the autistic brain. Instead, the frontal lobe closely resembles the temporal lobe. Most of the features that normally distinguish the two regions had disappeared."

Two other clear-cut patterns emerged when the scientists compared the autistic and healthy brains. First, the autistic brain showed a drop in the levels of genes responsible for neuron function and communication. Second, the autistic brain displayed a jump in the levels of genes involved in immune function and inflammatory response.

"Several of the genes that cropped up in these shared patterns were previously linked to autism," said Geschwind. "By demonstrating that this pathology is passed from the genes to the RNA to the cellular proteins, we provide evidence that the common molecular changes in neuron function and communication are a cause, not an effect, of the disease."

The next step will be for the research team to expand its search for the genetic and related causes of autism to other regions of the brain.

Autism is a complex brain disorder that strikes in early childhood. The disease disrupts a child's ability to communicate and develop social relationships and is often accompanied by acute behavioral challenges. In the United States, autism spectrum disorders are diagnosed in one in 110 children — and one in 70 boys. Diagnoses have expanded tenfold in the last decade.

The study was funded by the National Institute of Mental Health, the Canadian Institutes of Health Research, and Genome Canada. Tissue samples were provided by the Autism Tissue Project, the Harvard Brain Bank and the Medical Research Council's London Brain Bank for Neurodegenerative Disease.
Geschwind's and Voineagu's co-authors included Jennifer Lowe, Yuan Tian, Steve Horvath, Jonathan Mill, Rita Cantor and Benjamin Blencowe of UCLA; Xinchen Wang of the University of Toronto; and Patrick Johnston of King's College London.