Post-treatment of a BiP inducer prevents cell death after middle cerebral artery occlusion in mice.

We previously reported the effect of a selective inducer of BiP (a BiP inducer X; BIX) after permanent middle cerebral artery occlusion (MCAO) in mice. However, in acute stroke, almost all drugs have been used clinically after the onset of events. We evaluated the effect of post-treatment of BIX after permanent MCAO in mice, and examined its neuroprotective properties in in vivo mechanism. BIX (intracerebroventricular injection at 20μg) administered either at 5min or 3h after occlusion reduced both infarct volume and brain swelling, but at 6h after occlusion there was no reduction. BIX protected against the decrease in a dose-dependent manner. Furthermore, BIX reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells induced by the ischemia in ischemic penumbra. These findings indicate that post-treatment with BIX after ischemia has neuroprotective effects against acute ischemic neuronal damage in mice even when given up to 3h after MCAO. BIX may therefore be a potential drug for stroke.