Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage.
J Cereb Blood Flow Metab
; 43(4): 531-541, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36545833
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Isquemia Encefálica
Limite:
Animals
Idioma:
En
Revista:
J Cereb Blood Flow Metab
Ano de publicação:
2023
Tipo de documento:
Article