Activation of Neuronal Ras ‐Related C3 Botulinum Toxin Substrate 1 (Rac1) Improves Post‐Stroke Recovery and Axonal Plasticity in Mice

AbstractLong ‐term disability after stroke is common but the mechanisms of post‐stroke recovery is unclear. Cerebral Ras‐related C3 botulinum toxin substrate (Rac) 1 contributes to functional recovery after ischemic stroke in mice. As Rac1 plays divergent roles in individual cell types after central neural system injury, we herein examined the specific role of neuronal Rac1 in post‐stroke recovery and axonal regeneration. Young male mice were subjected to 60‐minutes middle cerebral artery occlusion (MCAO). Inducible deletion of neuronal Rac1 by daily intraperitoneal injection of tamoxifen (2 mg/4 0 g) into Thy1‐creER/Rac1‐floxed mice day 7‐11 after MCAO worsened cognitive (assayed by novel object recognition test) and sensorimotor (assayed by adhesive removal and pellet reaching tests) recovery day 14‐28 accompanied with the reduction of neurofilament‐L (NFL) and myelin basic prote in (MBP) and the elevation of glial fibrillary acidic protein (GFAP) in the peri‐infarct zone assessed by immunostaining. Whereas the brain tissue loss was not altered assayed by cresyl violet staining. In another approach, delayed overexpression of neuronal Rac1 by injection of lentivirus encodin g Rac1 with neuronal promotor into both the cortex and striatum (total 4 μl at 1×109 transducing units/mL) of stroke side in C57BL/6J mice day 7 promoted stroke outcome, NFL and MBP regrowth and alleviated GFAP invasion. Furthermore, neuronal Rac1 overexpression led to the activati...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research