Impact of insufficient recovery of cerebral blood flow due to partial reperfusion on the pathophysiology of ischemic stroke in mice

• DOI: 10.1016/j.neulet.2023.137370
• Publication Date: 2023-07-01T15:13:25Z
• Authors: Munehisa Shimamura; Chin yang Chang; Hiroki Hayashi; Satoshi Baba; Shota Yoshida; Hironori Nakagami
• Keywords: Stroke; Mice; Cerebrovascular Circulation; Reperfusion; Animals; Brain; Infarction, Middle Cerebral Artery; 3. Good health; Ischemic Stroke; Brain Ischemia

Recent advances in endovascular treatment (EVT) dramatically changed the outcome of ischemic stroke, but partial reperfusion does not improve the outcome as well as no reperfusion. Although partial reperfusion is estimated to be more potential for therapeutic intervention than permanent occlusion due to some blood supply, their pathophysiological difference is still unknown. To answer the question, we analyzed the difference in mice, which were exposed to distal middle cerebral artery occlusion with 14-min common carotid artery (CCA) occlusion (partial reperfusion) or permanent CCA occlusion (no reperfusion). Although the final infarct volume was same between permanent and partial reperfusion, Fluoro-jade C staining showed that neurodegeneration was inhibited both in the severe and moderate ischemic region 3 h after partial reperfusion. Also, partial reperfusion increased the number of TUNEL-positive cells only in the severe ischemic region. IgG extravasation was suppressed at 24 h only in the moderate ischemic region in partial reperfusion. Injected FITC-dextran was observed in the brain parenchyma with BBB leakage at 24 h in partial reperfusion, but not in permanent occlusion. The expression of il1β and il6 mRNA was inhibited in the severe ischemic region. Thus, partial reperfusion showed region-dependent favorable pathophysiology, such as delayed neurodegeneration, suppressed BBB destruction and inflammation, and potential for drug delivery, when compared to permanent occlusion. Further studies on the molecular differences and effectiveness of drugs will shed light on the development of novel treatments for partial reperfusion in ischemic stroke.