Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage

Cerebral ischemia triggers inflammatory changes, and early complications and unfavorable outcomes of endovascular thrombectomy for brain occlusion promote the recruitment of various cell types to the ischemic area. Although anti-inflammatory M2-type macrophages are thought to exert protective effects against cerebral ischemia, little has been clarified regarding the significance of post-ischemic phase-dependent modulation of M2-type macrophages. To test our hypothesis that post-ischemic phase-dependent modulation of macrophages represents a potential therapy against ischemic brain damage, the effects on rats of an M2-type macrophage-specific activator, Gc-protein macrophage-activating factor (GcMAF), were compared with vehicle-treated control rats in the acute (day 0–6) or subacute (day 7–13) phase after ischemia induction. Acute-phase GcMAF treatment augmented both anti-inflammatory CD163+M2-type- and pro-inflammatory CD16+ M1-type macrophages, resulting in no beneficial effects. Conversely, subacute-phase GcMAF injection increased only CD163+ M2-type macrophages accompanied by elevated mRNA levels of arginase-1 and interleukin-4. M2-type macrophages co-localized with CD36+ phagocytic cells led to clearance of the infarct area, which were abrogated by clodronate-liposomes. Expression of survival-related molecules on day 28 at the infarct border was augmented by GcMAF. These data provide new and important insights into the significance of M2-type macrophage-specific activation as post-ischemic phase-dependent therapy.

内容要旨・審査要旨・論文本文の公開
本論文は，著者Yoshitaka Kurashikiの学位論文として提出され，学位審査・授与の対象となっている。

Kurashiki Y, Kagusa H, Yagi K, et al. Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage. Journal of Cerebral Blood Flow & Metabolism. 2023;43(4):531-541. Copyright © 2022 The Author(s). doi:10.1177/0271678X221147090