Initial reperfusion level determines brain infarct size after transient focal ischemia in mice

Abstract

P90 The intraluminal middle cerebral artery (MCA) thread occlusion model in mice was modified to allow reperfusion at different levels after an epsiode of 1 h transient focal cerebral ischemia. This was achieved by keeping the ipsilateral common carotid artery (CCA) either patent or ligated after thread withdrawal. Our aim was to examine to what extent the degree of initial reperfusion influences brain infarct evolution and neurological outcome. C57Black/6 mice were subjected to 1 h MCA occlusion, followed by 0, 1,3, 6, 24, and 72 h reperfusion, with ligated or open CCA (n=4/group). Prior to termination of the experiment by in situ freezing with liquid nitrogen, cerebral protein synthesis (CPS) and blood flow (CBF) were measured simultaneously using H3-leucine and C14-iodoantipyrine, respectively. Multiparametric imaging of H3-CPS and C14-CBF was achieved by double tracer autoradiography, and regional ATP levels by bioluminescent imaging. ATP-depleted and CPS-suppressed areas were expressed as percentage of hemisphere. Relative CBF was calculated in the area of inhibited CPS and expressed as percent of the contralateral homotopic area. In addition, the neurological score of animals was monitored after reperfusion. At the end of ischemia, metabolic disturbances were the same in both experimental groups. After 1 h recirculation, ATP initially recovered despite lower relative CBF in the CCA-ligated (57±9%) as compared to the CCA open group (82 ± 12%; p