神经保护
冲程(发动机)
认知功能衰退
海马体
小胶质细胞
干细胞
生物
痴呆
神经科学
医学
免疫学
病理
炎症
细胞生物学
工程类
疾病
机械工程
作者
Lukasz Wlodarek,Faisal J. Alibhai,Jun Wu,Shuhong Li,Ren‐Ke Li
出处
期刊:Stem Cells
[Wiley]
日期:2022-03-15
卷期号:40 (6): 564-576
被引量:7
标识
DOI:10.1093/stmcls/sxac019
摘要
To date, stroke remains one of the leading causes of death and disability worldwide. Nearly three-quarters of all strokes occur in the elderly (>65 years old), and a vast majority of these individuals develop debilitating cognitive impairments that can later progress into dementia. Currently, there are no therapies capable of reversing the cognitive complications which arise following a stroke. Instead, current treatment options focus on preventing secondary injuries, as opposed to improving functional recovery.We reconstituted aged (20-month old) mice with Sca-1+ bone marrow (BM) hematopoietic stem cells isolated from aged or young (2-month old) EGFP+ donor mice. Three months later the chimeric aged mice underwent cerebral ischemia/reperfusion by bilateral common carotid artery occlusion (BCCAO), after which cognitive function was evaluated. Immunohistochemical analysis was performed to evaluate host and recipient cells in the brain following BCCAO.Young Sca-1+ cells migrate to the aged brain and give rise to beneficial microglial-like cells that ameliorate stroke-induced loss of cognitive function on tasks targeting the hippocampus and cerebellum. We also found that young Sca-1+ cell-derived microglial-like cells possess neuroprotective properties as they do not undergo microgliosis upon migrating to the ischemic hippocampus, whereas the cells originating from old Sca-1+ cells proliferate extensively and skew toward a pro-inflammatory phenotype following injury.This study provides a proof-of-principle demonstrating that young BM Sca-1+ cells play a pivotal role in reversing stroke-induced cognitive impairments and protect the aged brain against secondary injury by attenuating the host cell response to injury.
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