Post-acute phase Rac1 activation promotes long-term recovery of ischemic stroke via the Pak1/p38/β-catenin pathway.

Tremendous advances have been made in the understanding of neurogenesis in the adult brain, which offers hope for therapeutic strategies that target neurogenesis in the repair of nerve damage after stroke. Rac1 plays a key role in the neurogenesis of the central nervous system as one of the small GTPase members of the Rho family. However, the role of Rac1 after ischemic stroke remains controversial. This may be due to its role in mediated production of harmful substances such as ROS during the acute phase. Therefore, we are trying to explore whether it can play a role in nerve repair after the acute phase. Our research indicates that the activation of Rac1 in the post-acute phase supports ischemic recovery. Specifically, intraventricular injection of a Rac1 activator one week after middle cerebral artery occlusion (MACO) improved brain atrophy and neurological function. Rac1 activation induced the migration of neural stem cells in vitro and promoted their migration in vivo, aiding in their differentiation into mature neurons. Results from Western blotting and Co-immunoprecipitation (Co-IP) assaysuggest that Rac1 activation promotes the migration and differentiation of neural stem cells through the downstream Pak1/p38/β-catenin signaling pathway. Furthermore, Rac1 activation promotes post-stroke vascular regeneration and synaptic remodeling, In conclusion, the activation of Rac1 in the post-acute phase promotes neural repair following stroke, indicating its potential as a therapeutic target during the recovery phase of ischemic stroke.