A modified mini-stroke model with region-directed reperfusion in rat cortex.

Abstract

Mini-ischemia localized into a specific brain area has promoted understanding of the mechanisms underlying brain recovery in stroke. However, the conventional mini-stroke model adopted permanent arterial ligations but lacked controllable reperfusion, which is crucial for the outcome of delayed functional recovery. In this study, we devised a new rat mini-stroke model in which the vascular ligations can be easily reversed to induce targeted reperfusion. Specifically, a flexible ring was incorporated into the conventional small arterial ligations to tighten the ligating loops and facilitate cutting the ligatures for sufficient reperfusion afterwards. The distribution of cerebral blood flow was explored directly through a cranial window using laser speckle contrast imaging. A distinct ischemic core, which well fits the profile of the ligated ring, was bordered by a penumbral zone and then together surrounded by nonischemic tissue immediately after the arterial ligations involving the ring. After cutting the ligatures, post-recanalization hyperperfusion occurred in the previous ischemic core and to a greater extent at 24 h after reperfusion. In contrast, recirculation of common carotid artery in the conventional mini-stroke model hardly altered hypoperfusion status within the ischemic core. Evidence from two kinds of control groups indicated that the ring might produce a compression effect on the underlying cortex and then contribute to the more highly localized infarct that was identified by triphenyltetrazolium chloride staining. Our data suggest that this model provides opportunities for investigating the neurovascular dynamics in acute stroke and rehabilitation, especially with emerging optical imaging techniques.