The study, published inthe Journal of Cerebral Blood Flow and Metabolism, sheds light on the possible mechanisms behind the suggested neuroprotective effects of alpha-tocotrienol after stroke by helping to retain important transcripts that are usually lost during an stroke event.
Professor Chandan Sen from Ohio State University, USA, the research team used a variety of animal and cell studies to confirm that loss of the microRNA precursor (miR29) plays an important role in the development of stroke-induced neuronal injuries - adding that the vitamin E compound alpha-tocotrienol prevented these losses at the infarct site and so offered protection against neural damage.
“Micro RNAs (miR) are small non-coding RNA molecules that play important role in regulating gene expression at the translation level, and miR29 is the micro RNA in the study of stroke etiology and in many other neurodegenerative disorders including Alzheimer’s Disease,” explained Dr Savita Khanna - a co-researcher on the study.
"Oral supplementation of a-tocotrienol was effective in completely rescuing stroke-induced loss of both miR-29b as well as miR-29c," said the researchers. "Such effect was associated with protection against stroke-induced lesion in the brain."
Sen and colleagues used a mouse model of stroke in which the mice were subjected to temporary middle-cerebral artery occlusion (MCAO) to induce stroke. At 48 hours after MCAO, there was a significant loss of miR29b at the infarct site, they confirmed.
By re-introducing miR29b at the infarct site, the team then showed that it was possible to decrease stroke-induced brain lesions by half - as compared to a control where no miR29b was reintroduced.
They noted that miR29b also significantly improved post-stroke sensorimotor functions, meaning that the group of mice that received miR29b has better agility and movement 48 hours post stroke, compared to control.
Sen then tested the effect of alpha-tocotrienol in the same mouse stroke model - giving mice 50mg/kg body weight of alpha-tocotrienol (Tocomin, Carotech Inc.) or a control that consisted of vitamin E stripped corn oil for 10 weeks before subjecting them to MCAO.
Results showed that stroke-induced loss of miR29b was completely spared in the tocotrienol supplemented group, which resulted in smaller lesion size.
Commenting on the research, WH Leong, vice president of Carotech Inc said that the findings "further strengthens the science of Tocomin for neuroprotection."
"In a stroke event, neuroprotective miR29b is loss due to the downstream product of 12-Lipoxygenase (12-Lox) called 12HETE, which leads to neuronal cell death. Tocomin is able to rescue miR29b by inhibiting 12-Lox,” he said.
Source: Journal of Cerebral Blood Flow and Metabolism
Published online ahead of print, doi: 10.1038/jcbfm.2013.68
" Loss of miR-29b following acute ischemic stroke contributes to neural cell death and infarct size"
Authors: Savita Khanna, et al