The effects of rapamycin on the symptoms of cerebral ischemia due to changing the expression of miR-1 and its target genes, Bad and Bcl-w

Introduction: Stroke is the major cause of long-term disability in adults. The precise role of the mTOR signaling pathway in neural viability due to rapamycin effect in the animal model of middle cerebral artery occlusion (MCAO) remained elusive. Since the relationship between mTOR and miR-1, especially in neurons, is unknown, we have evaluated the effect of rapamycin as a post-ischemic treatment on improving stroke symptoms. Methods: Rats were divided into three groups including sham, control and rapamycin treatment group. Each contains four subgroups (n=7). One hour after MCAO, rats were received intravenously 0.1ml normal saline or 0.1ml rapamycin in the control and treatment groups, respectively. After 24 hours, neurologic deficit score, infarct volume, brain edema, and blood-brain barrier (BBB) permeability were measured in the control and treatment group. The expression of miR-1, Bcl-w and Bad were analyzed using quantitative RT-PCR in all groups. Results: Our results indicate that post-treatment with rapamycin, significantly reduces neurological deficits, infarct volume, brain edema and BBB permeability. It also decreases the level of miR-1 and Bad expression and increases the level of Bcl-w expression. Conclusion: According to our findings, post-ischemic treatment with rapamycin can be effective in improving symptoms of stroke using changing in the expression of the miR-1 gene and consequently, a changing in the expression of the target genes of this miRNA (i.e., Bad and Bcl-w). In summary, we unravel for the first time a link between mTOR, miRNA-1, Bcl-w and Bad in brain ischemia.