Laboratory of Experimental Stroke Research, Department of Surgery and Translational Medicine, University of Milano Bicocca, Monza, Italy; Milan Center for Neuroscience (NeuroMi), Milano, Italy.
Laboratory of Experimental Stroke Research, Department of Surgery and Translational Medicine, University of Milano Bicocca, Monza, Italy; PhD Programme in Neuroscience, University of Milano Bicocca, Monza, Italy.
Neurobiol Dis. 2015 Feb;74:305-13. doi: 10.1016/j.nbd.2014.11.019. Epub 2014 Dec 5.
Intracranial collaterals are dynamically recruited after arterial occlusion and are emerging as a strong determinant of tissue outcome in both human and experimental ischemic stroke. The relationship between collateral flow and ischemic penumbra remains largely unexplored in pre-clinical studies. The aim of the present study was to investigate the pattern of collateral flow with regard to penumbral tissue after transient middle cerebral artery (MCA) occlusion in rats. MCA was transiently occluded (90min) by intraluminal filament in adult male Wistar rats (n=25). Intracranial collateral flow was studied in terms of perfusion deficit and biosignal fluctuation analyses using multi-site laser Doppler monitoring. Molecular penumbra was defined by topographical mapping and quantitative signal analysis of Heat Shock Protein 70kDa (HSP70) immunohistochemistry. Functional deficit and infarct volume were assessed 24h after ischemia induction. The results show that functional performance of intracranial collaterals during MCA occlusion inversely correlated with HSP70 immunoreactive areas in both the cortex and the striatum, as well as with infarct size and functional deficit. Intracranial collateral flow was associated with reduced areas of both molecular penumbra and ischemic core and increased areas of intact tissue in rats subjected to MCA occlusion followed by reperfusion. Our findings prompt the development of collateral therapeutics to provide tissue-saving strategies in the hyper-acute phase of ischemic stroke prior to recanalization therapy.
颅内侧支循环在动脉闭塞后被动态募集，并且在人类和实验性缺血性卒中都成为组织结局的一个重要决定因素。在临床前研究中，侧支血流与缺血半影区之间的关系在很大程度上仍未得到探索。本研究旨在探讨大鼠短暂性大脑中动脉（MCA）闭塞后侧支血流与半影区组织之间的关系。通过管腔内纤维丝将成年雄性 Wistar 大鼠的 MCA 短暂闭塞（90min）（n=25）。使用多点激光多普勒监测进行灌注缺损和生物信号波动分析，研究颅内侧支循环。通过热休克蛋白 70kDa（HSP70）免疫组织化学的拓扑映射和定量信号分析，定义分子半影区。在缺血诱导后 24 小时评估功能缺损和梗死体积。结果表明，MCA 闭塞期间颅内侧支循环的功能表现与皮质和纹状体中 HSP70 免疫反应性区域以及梗死体积和功能缺损呈负相关。MCA 闭塞后继发再灌注的大鼠，颅内侧支循环与分子半影区和缺血核心的面积减少以及完整组织的面积增加有关。我们的研究结果提示开发侧支治疗的策略，以在再通治疗前的缺血性卒中超急性期为组织提供保存策略。
