Department of Neurology, Aging and Neurodegenerative Disease Laboratory, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Department of Neurology, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Cell Death Dis. 2022 Jan 10;13(1):33. doi: 10.1038/s41419-021-04424-x.
Aged microglia display augmented inflammatory activity after neural injury. Although aging is a risk factor for poor outcome after brain insults, the precise impact of aging-related alterations in microglia on neural injury remains poorly understood. Microglia can be eliminated via pharmacological inhibition of the colony-stimulating factor 1 receptor (CSF1R). Upon withdrawal of CSF1R inhibitors, microglia rapidly repopulate the entire brain, leading to replacement of the microglial compartment. In this study, we investigated the impact of microglial replacement in the aged brain on neural injury using a mouse model of intracerebral hemorrhage (ICH) induced by collagenase injection. We found that replacement of microglia in the aged brain reduced neurological deficits and brain edema after ICH. Microglial replacement-induced attenuation of ICH injury was accompanied with alleviated blood-brain barrier disruption and leukocyte infiltration. Notably, newly repopulated microglia had reduced expression of IL-1β, TNF-α and CD86, and upregulation of CD206 in response to ICH. Our findings suggest that replacement of microglia in the aged brain restricts neuroinflammation and brain injury following ICH.
衰老的小胶质细胞在神经损伤后表现出增强的炎症活性。虽然衰老是脑损伤后预后不良的一个风险因素，但衰老相关的小胶质细胞改变对神经损伤的确切影响仍知之甚少。小胶质细胞可以通过抑制集落刺激因子 1 受体（CSF1R）的药理学抑制来消除。CSF1R 抑制剂撤回后，小胶质细胞迅速在整个大脑中重新定植，导致小胶质细胞区室的替换。在这项研究中，我们使用胶原酶注射诱导的脑内出血（ICH）的小鼠模型，研究了衰老大脑中小胶质细胞替换对神经损伤的影响。我们发现，衰老大脑中小胶质细胞的替换减少了 ICH 后的神经功能缺损和脑水肿。小胶质细胞替换诱导的 ICH 损伤减轻伴随着血脑屏障破坏和白细胞浸润的减轻。值得注意的是，新定植的小胶质细胞在 ICH 后表现出 IL-1β、TNF-α 和 CD86 的表达降低，以及 CD206 的上调。我们的研究结果表明，衰老大脑中小胶质细胞的替换限制了 ICH 后的神经炎症和脑损伤。
