Effect of the administration of astrocyte- and endothelial cell-derived exosomes on the restoration of the blood-brain barrier and locomotion in an ischemia-reperfusion event.

Background:Cerebrovascular events (CVE) are the leading cause of neurological disorders and mortality worldwide. The ischemic type significantly disrupts the blood-brain barrier (BBB), particularly affecting tight junction proteins, leading to brain damage and motor dysfunction. Current treatments focus on restoring blood flow but are limited by a narrow therapeutic window and risks. Exosomes derived from neural cells have shown potential in neuroprotection, particularly in BBB repair, but their mechanisms remain largely unexplored.Objective:To determine the role of astrocyte- and endothelial cell-derived exosomes in restoring the BBB and improving locomotion in an ischemia/reperfusion model.Methodology:The study involves primary cultures of astrocytes and endothelial cells from Wistar rats to isolate exosomes. These will be administered to a middle cerebral artery occlusion (MCAO) model in mice. The research will evaluate exosome effects on tight junction proteins (Claudin-5, ZO-1, and Ocludin), hippocampal neuronal structure, and motor function using locomotion assessments and neuroimaging techniques. The project will be conducted at the Pharmacology Laboratory of the University of Guadalajara and CINVESTAV.Expected Impact:The findings could provide a novel therapeutic approach for post-ischemic recovery, focusing on BBB integrity and functional rehabilitation.