RNA interference-mediated downregulation of Beclinl attenuates cerebral ischemic injury in rats

Aim： To test the role of the Beclin 1-dependent autophagy pathway in brain damage during cerebral ischemia. Methods： Focal cerebral ischemia was established in rats using a middle cerebral artery occlusion （MCAO） model. A lentiviral vectorassociated RNA interference （RNAi） system was stereotaxically injected into the ipsilateral lateral ventricle to reduce Beclinl expression. We measured the ipsilateral infarct volume, autophagosome formation, neurogenesis and apoptosis, all of which could be modulated by Beclinl RNAi. Results： On the 14th day after MCAO, Beclinl downregulation by RNAi increased the population of neural progenitor cells （BrdU^＋-DCX^＋）, newborn immature cells （BrdU^＋-Tuj-1^＋） and mature neurons （BrdU^＋-MAP-2^＋）, and reduced the apoptosis of immature neurons （caspase- 3^＋-DCX^＋ and caspase-3^＋Tuj-1^＋） surrounding the ischemic core of the ipsilateral hemisphere. Furthermore, RNAi-mediated downregulation of Beclinl decreased infarct volume and inhibited histological injury and neurological deficits. Conclusion： RNAi-mediated downregulation of Beclinl improves outcomes after transient MCAO.