Activation of neuronal Ras ‐related C3 botulinum toxin substrate 1 (Rac1) improves post‐stroke recovery and axonal plasticity in mice

We propose that activation of neuronal Rac1 mediates the release of BDNF via PAK1 signaling, which further promotes axonal plasticity and alleviates astrogliosis, and eventually contributes to functional recovery after brain ischemia. Targeting neuronal Rac1 may offer a potential therapeutic target for promoting brain remapping and functional recovery after stroke. AbstractLong-term disability after stroke is common but the mechanisms of post-stroke recovery remain 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-min of middle cerebral artery occlusion (MCAO). Inducible deletion of neuronal Rac1 by daily intraperitoneal injection of tamoxifen (2  mg/40 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 prot ein (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, delay...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research