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ID 118878
タイトル別表記
脳梗塞モデルラットにおける虚血後の時期依存的な抗炎症性M2マクロファージ活性化変調の役割
著者
倉敷, 佳孝 徳島大学大学院医学研究科(医学専攻)
木内, 智也 Tokushima University
住吉, 学 Tokushima University
Kitazato, Keiko T Tokushima University
キーワード
Arginase-1
cerebral ischemia
interleukin-4
macrophage modulation
post-ischemic phase
資料タイプ
学位論文
抄録
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.
掲載誌名
Journal of Cerebral Blood Flow & Metabolism
ISSN
15597016
0271678X
cat書誌ID
AA12510484
AA10458430
出版者
International Society for Cerebral Blood Flow and Metabolism|Sage
43
4
開始ページ
531
終了ページ
541
発行日
2022-12-22
備考
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。
権利情報
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
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3766号
学位記番号
甲医第1591号
学位授与年月日
2023-12-28
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系
生物資源系