Using Older Mice, Researchers Find Potential Stroke Prevention Agent

Using older mice, researchers looking for ways to prevent stroke found a protective effect in bexaratone. The age of the mice is significant in that most studies are done on young animals and findings might not apply to mice that have aged.

A mouse study in Finland showed that bexaratone had a neuroprotective effect. The findings could prove useful in stroke prevention.

A novel and significant part of the study is that the research was done using mice of advanced age and with tauopathy with ischemic thromboembolic cerebral ischemia.

They also identified a new autophagy-modulating effect. The study was conducted by Mikko Huuskonen, of the Department of Neurobiology at AI Virtanen Institute for Molecular Sciences, part of the University of Finland in Kuopio, Finland, and colleagues. It was published in the journal Nature on September 14, 2016.

The researchers assert that, although the majority of stroke occurs in elderly people who often have comorbidities such as dementia, most preclinical studies are performed in young, healthy mice. They note that “neurofibrillary tangles (NFT), which are aggregates of hyperphosphorylated protein tau, are a universal feature of older individual’s brains.”

They go on to suggest that “this may be one causative factor explaining the poor translation of preclinically successful drugs in human clinical trials.”

Thus, the researchers “investigated the neuroprotective effect of bexarotene in a co-morbidity model of stroke that combines high age and tauopathy with thromboembolic cerebral ischemia.”

Their findings were two-fold.

First, they say, “Our results indicate for the first time that bexarotene is protective in a clinically relevant murine model involving aging, thromboembolic stroke and tauopathy.”

Secondly, they add, “We also demonstrate a novel autophagy-modulating effect of bexarotene in a neuronal cells and report that bexarotene restores defective mitochondrial respiration in neurons carrying the P301L-tau mutation.”

The authors conclude by saying, “Because dysregulation of autophagy is observed in several neurodegenerative conditions, our results call for further studies to investigate whether bexarotene modulates the autophagic process in these diseases.”

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