Microglia depletion increase brain injury after acute ischemic stroke in aged mice.
Microglia depletion increase brain injury after acute ischemic stroke in aged mice.
复制标题
小鼠急性缺血性中风后，小胶质细胞耗竭会增加脑损伤。
DOI：
10.1016/j.expneurol.2020.113530
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Chauhan A
中科院分区：
文献类型：
--
作者：
Marino Lee S;Hudobenko J;McCullough LD;Chauhan A
小胶质细胞是缺血性损伤的第一反应者之一。中风后，老年小胶质细胞获得衰老表型并产生更多的炎症细胞因子。年轻小鼠中小胶质细胞的消耗通过增加炎症来减轻缺血后损伤。然而，年轻的小鼠没有功能失调的小胶质细胞。因此，我们假设老年小鼠小胶质细胞的耗竭将有助于改善缺血性中风损伤后的早期恢复。用对照食物饮食（CD）或PLX 5622食物饮食（PLXD）喂养老年（18-19月龄）小鼠21天。在第22天，进行60分钟的大脑中动脉闭塞（MCAo）手术或假手术。卒中后24和72小时进行免疫组织化学和流式细胞术。使用抗CSF 1 R的单克隆抗体AFS 98通过注射到右半球来特异性地消耗脑巨噬细胞。在AFS 98注射后两天，小鼠经历1小时MCAo。24小时后，将小鼠安乐死并进行流式细胞术。老年小鼠中风后24和72小时，PLXD与CD相比，梗死体积增加（p<0.05）。在老年中风小鼠中，在小胶质细胞耗竭后观察到浸润单核细胞的增加（p<0.05），这表明单核细胞应答不同。与CD假手术相比，PLXD假手术小鼠中星形胶质细胞数量明显增加，反映了PLX 5622治疗的脱靶效应。总之，PLX 5622和AFS 98治疗耗尽了老年动物中的小胶质细胞，但导致缺血性卒中后神经炎症增加。
Microglia are one of the first responders to ischemic injury. Aged microglia acquire a senescent phenotype and produce more inflammatory cytokines after stroke. Depletion of microglia in young mice worsens post-ischemic damage by increasing inflammation. However, young mice do not have dysfunctional microglia. Hence, we hypothesized that depletion of microglia in older mice will contribute to improved early recovery after ischemic stroke injury. Aged (18–19 month) mice were fed with either control chow diet (CD) or PLX5622 chow diet (PLXD) for 21 days. On day 22, a 60-minute middle cerebral artery occlusion (MCAo) surgery or sham surgery was performed. Twenty-four and 72 hours after stroke immunohistochemistry and flow cytometry were performed. AFS98, a monoclonal antibody against CSF1R was used to specifically deplete brain macrophages by injection into the right hemisphere. Two days after AFS98 injections, mice underwent one-hour MCAo. Twenty-four hours later mice were euthanized and flow cytometry was performed. An increase in infarct volume (p<0.05) was seen in the PLXD versus CD after stroke in aged mice at 24 and 72 hours. An increase (p<0.05) in infiltrating monocytes was observed after microglial depletion in aged stroke mice suggesting a differential monocyte response. An increase in astrocyte numbers was evident in the PLXD sham mice compared to CD sham, reflecting the off-target effects of PLX5622 treatment. In conclusion, PLX5622 and AFS98 treatment depleted microglia in aged animals but resulted in increased neuroinflammation after ischemic stroke.
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影响因子：
16.6
作者：
Szalay G;Martinecz B;Lénárt N;Környei Z;Orsolits B;Judák L;Császár E;Fekete R;West BL;Katona G;Rózsa B;Dénes Á
通讯作者：
Dénes Á
影响因子：
12.7
作者：
Otxoa-de-Amezaga, Amaia;Miro-Mur, Francesc;Planas, Anna M.
通讯作者：
Planas, Anna M.
影响因子：
4.2
作者：
Chauhan A;Al Mamun A;Spiegel G;Harris N;Zhu L;McCullough LD
通讯作者：
McCullough LD
影响因子：
168.9
作者：
Feigin, Valery L.;Forouzanfar, Mohammad H.;Krishnamurthi, Rita;Mensah, George A.;Connor, Myles;Bennett, Derrick A.;Moran, Andrew E.;Sacco, Ralph L.;Anderson, Laurie;Truelsen, Thomas;O'Donnell, Martin;Venketasubramanian, Narayanaswamy;Barker-Collo, Suzanne;Lawes, Carlene M. M.;Wang, Wenzhi;Shinohara, Yukito;Witt, Emma;Ezzati, Majid;Naghavi, Mohsen;Murray, Christopher
通讯作者：
Murray, Christopher
影响因子：
15.1
作者：
Sosna J;Philipp S;Albay R 3rd;Reyes-Ruiz JM;Baglietto-Vargas D;LaFerla FM;Glabe CG
通讯作者：
Glabe CG