RESUMO
Inflammation is an essential component for glial scar formation. However, the upstream mediator(s) that triggers the process has not been identified. Previously, we showed that the expression of CD36, an inflammatory mediator, occurs in a subset of astcotyes in the peri-infarct area where the glial scar forms. This study investigates a role for CD36 in astrocyte activation and glial scar formation in stroke. We observed that the expression of CD36 and glial fibrillary acidic protein (GFAP) coincided in control and injured astrocytes and in the brain. Furthermore, GFAP expression was attenuated in CD36 small interfering RNA transfected astrocytes or in the brain of CD36 knockout (KO) mice, suggesting its involvement in GFAP expression. Using an in-vitro model of wound healing, we found that CD36 deficiency attenuated the proliferation of astrocytes and delayed closure of the wound gap. Furthermore, stroke-induced GFAP expression and scar formation were significantly attenuated in the CD36 KO mice compared with wild type. These findings identify CD36 as a novel mediator for injury-induced astrogliosis and scar formation. Targeting CD36 may serve as a potential strategy to reduce glial scar formation in stroke.
Assuntos
Astrócitos/metabolismo , Antígenos CD36/metabolismo , Cicatriz/metabolismo , Gliose/metabolismo , Acidente Vascular Cerebral/patologia , Animais , Astrócitos/imunologia , Astrócitos/patologia , Antígenos CD36/genética , Técnicas de Cultura de Células , Linhagem Celular , Proliferação de Células , Cicatriz/patologia , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida , Gliose/patologia , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/metabolismo , Neuroglia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/metabolismoRESUMO
Although infiltration of peripheral monocytes/macrophages is implicated in stroke pathology, in vivo data regarding the deployment of monocytes and their mobilization to the infarct area is scarce. Recent literature showed that mouse monocytes exhibit two distinct populations that represent pro-inflammatory (Ly-6Chi/CCR2+) and anti-inflammatory (Ly-6Clow/CCR2-) subsets and that spleen is a major source for monocyte deployment upon injury. By reducing post-ischemic infection with antibacterial moxifloxacin (MFX) treatment, the present study investigates the effect of the treatment on Ly-6C and CCR2 expression in the spleen following ischemia and the extent to which the effect is associated with attenuation of post-ischemic inflammation and injury. Mice subjected to a middle cerebral artery occlusion (MCAO) showed a significant reduction in their spleen weights compared to sham animals. Compared to vehicle controls, splenocytes obtained from daily MFX-treated mice 7 days after ischemia exhibited significantly reduced mean Ly-6C expression within pro-inflammatory subsets, whereas the distribution of pro- and anti-inflammatory subsets was not different between the treatment groups. Additionally, MFX treatment significantly reduced CCR2 expression in the spleen tissue and in the post-ischemic brain and attenuated infarct size. The study suggests a potential contributing role of spleen monocytes in post-ischemic inflammation and injury. The influence of peripheral inflammatory status on the primary injury in the CNS further implies that the attenuation of post-stroke infection may be beneficial in mitigating stroke-induced brain injury.
