Preventive Use of One Form of Natural Vitamin E May Reduce Stroke Damage

Scientists looking at other stroke interventions that could easily translate into clinical practice

Newswise — COLUMBUS, Ohio –Preventive supplementation with a natural form of vitamin E called tocotrienol could help reduce brain damage caused by strokes, researchers reported today at the 2nd International Conference on Tocotrienols and Chronic Diseases. The scientists also found evidence that tocotrienol may trigger genes that alter blood vessel structure to help bypass a blockage, and may help prevent a repeat stroke, which occurs in about 200,000 people each year.

Supported by funding from The Ohio State University Center for Clinical and Translational Science (CCTS), the findings add to a growing body of work by a team of stroke researchers studying therapies that can be easily adopted by physicians.

“There is a lot of promising research to develop compounds that target chemicals in the brain to reduce stroke damage, but it will be years before we see an actual drug,” says Dr. Cameron Rink, and one of the key tocotrienol researchers. “We’ve been focusing on simple damage reducing strategies – such as prophylactic use of a rare form of vitamin E and oxygen therapy - which could be quickly implemented into clinical practice.”

Tocotrienol reduces stroke damage in multiple waysResearchers at Ohio State have been studying the impact of tocotrienol vitamin E on brain tissue for more than a decade. Tocotrienol, also known as TCT, represents half of the naturally occurring vitamin E family. While TCT is a common component of a typical Southeast Asian diet, it is not found in Western (American) diet, where it is available as a nutritional supplement. For the study, 20 dogs were randomly assigned to either receive a placebo or a TCT supplement daily for 10 weeks. Scientists then induced stroke by blocking an artery in the animals’ brains for one hour while the animals were under anesthesia.

Researchers found that 24 hours after a stroke, lesions indicating brain tissue damage were about 80 percent smaller in dogs that received TCT supplementation in comparison to the dogs that received no intervention. Imaging tests showed that the treated animals’ brains also had better blood flow at the stroke site.

Additional examination of brain tissue showed that the TCT supplementation appeared to support arteriogenesis, a process by which collateral arteries remodel themselves into larger vessels so they can bypass the site of blockage. Genes associated with this process were more active in the affected brain tissue from TCT treated dogs than were those from untreated dogs. Researchers note that brain function in humans and large mammals such as dogs is similar, making the results even more impactful. “This is one of the first studies to provide evidence that a safe nutrient – a vitamin – can improve blood flow in the stroke-affected brain,” says Cameron Rink, associate professor of surgery and study co-investigator.

Researchers also say the findings suggest that use of TCT could be particularly helpful to people who have previously suffered a mini-stroke, also known as a transient ischemic attack (TIA). TIA patients are at high-risk for developing a second, more severe stroke. Of the estimated 800,000 strokes each year; roughly 25 percent are repeat events, according to the American Heart Association. The results of this study offer the last piece of evidence needed prior to testing TCT’s protection against stroke in humans. A phase II trial of its effectiveness in humans is in the planning stages.

The research is published online and is scheduled for future print publication in the Journal of Cerebral Blood Flow & Metabolism.

Timing of oxygen supplementation key to reducing stroke damageIn a second separate study, the research team determined that glutamate, a neurotoxic factor during a stroke, could be changed into a neuroprotectant with the simple administration of oxygen.

“During stroke, blood vessels in the brain are blocked and vital blood-borne products, such as oxygen and glucose, are not able to reach the brain,” explains Savita Khanna, assistant professor of surgery at Ohio State who was awarded a pilot grant from the CCTS to look at the role of glutamate in brain injury. “In this oxygen-starved state, the brain releases excessive amounts of glutamate, which further damages brain tissue. We wanted to find out if there was a way to control that damage.”

The data, published in Journal of Cerebral Blood Flow & Metabolism (February 2010), showed that when oxygen therapy was given during stroke-induced hypoxia and before the introduction of clot-busting drugs, there was less brain damage. However, when oxygen therapy was applied after removing the blockage and blood flow was restored, damage was more severe.

“It appears that there may be a limited therapeutic window of opportunity for oxygen therapy – but if we can figure out what that window is – oxygen therapy can easily transition to a clinical setting without excessive cost to healthcare,” Khanna says.

Her research is also the first to show that supplemental oxygen turns on a protective factor, glutamate oxaloacetate transaminase (GOT), which helps metabolize glutamate to generate energy under low glucose conditions. This lowers the levels of toxic glutamate and supplies energy to the affected tissue during stroke, turning the glutamate into a neuroprotectant.

Based on this research, Khanna is pursuing additional NIH funding to develop therapeutic oxygen strategies to reduce stroke-related brain damage.

About The Ohio State University Center for Clinical and Translational ScienceDedicated to turning the scientific discoveries of today into the life-changing health innovations of tomorrow, The Ohio State University Center for Clinical and Translational Science (OSU CCTS) is a collaboration of experts including scientists and clinicians from seven OSU Health Science Colleges, OSU Medical Center and Nationwide Children’s Hospital. Funded by a multi-year Clinical and Translational Science Award (CTSA) from the National Institutes of Health, OSU CCTS provides financial, organizational and educational support to biomedical researchers as well as opportunities for community members to participate in credible and valuable research. For more information, visit http://ccts.osu.edu or contact: Kim Toussant ([email protected] 614-366-7215).