Depletion of microglia ameliorates white matter injury and cognitive impairment in a mouse chronic cerebral hypoperfusion model
Depletion of microglia ameliorates white matter injury and cognitive impairment in a mouse chronic cerebral hypoperfusion model
复制标题
DOI：
10.1016/j.bbrc.2019.05.055
复制
发表时间：
2019-07-05
影响因子：
3.1
通讯作者：
Kaneko, Shuji
中科院分区：
文献类型：
--
作者：
Kakae, Masashi;Tobori, Shota;Kaneko, Shuji
小胶质细胞是中枢神经系统(CNS)中的免疫细胞，对体内平衡至关重要，对神经保护和神经毒性都很重要，在多种中枢神经系统疾病中都被激活。小胶质细胞加重慢性脑低灌流所致的认知损害，但它们在这些条件下的确切作用尚不清楚。在这里，我们使用了一种集落刺激因子1受体抑制剂PLX3397来耗尽由双侧颈总动脉狭窄(BCAS)引起的慢性脑低灌流小鼠的小胶质细胞。在喂食含有PLX3397的食物的小鼠中，BCAS后28天引起的认知障碍显著改善。PLX3397组小鼠小胶质细胞减少，BCAS所致脑白质损伤受到抑制。此外，在喂饲PLX3397的小鼠中，促炎症细胞因子白介素6和肿瘤坏死因子α的表达受到抑制。综上所述，这些发现提示小胶质细胞在慢性脑低灌流所致的认知障碍和脑白质损伤的发生发展中起着破坏性的作用。因此，小胶质细胞是治疗慢性脑低灌注相关疾病的潜在靶点。(C)2019 Elsevier Inc.保留所有权利。
Microglia are immune cells in the central nervous system (CNS) and essential for homeostasis that are important for both neuroprotection and neurotoxicity, and are activated in a variety of CNS diseases. Microglia aggravate cognitive impairment induced by chronic cerebral hypoperfusion, but their precise roles under these conditions remain unknown. Here, we used PLX3397, a colony-stimulating factor 1 receptor inhibitor, to deplete microglia in mice with chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS). Cognitive impairment induced 28 days after BCAS was significantly improved in mice fed a diet containing PLX3397. In PLX3397-fed mice, microglia were depleted and white matter injury induced by BCAS was suppressed. In addition, the expression of proinflammatory cytokines, interleukin 6 and tumor necrosis factor alpha, was suppressed in PLX3397-fed mice. Taken together, these findings suggest that microglia play destructive roles in the development of cognitive impairment and white matter injury induced by chronic cerebral hypoperfusion. Thus, microglia represent a potential therapeutic target for chronic cerebral hypoperfusion-related diseases. (C) 2019 Elsevier Inc. All rights reserved.