星形胶质细胞对维持成年小鼠脑血脑屏障是必需的  

Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain

作　　者：Benjamin P Heithoff Kijana K George Aubrey N Phares Ivan A Zuidhoek Carmen Munoz-Ballester Stefanie Robel 杜一星(编译) Benjamin P Heithoff;Kijana K George;Aubrey N Phares;Ivan A Zuidhoek;Carmen Munoz-Ballester;Stefanie Robel(Fralin Biomedical Research Institute at Virginia Tech Carilion,Roanoke,Virginia,USA.;Department of Biological Sciences,Virginia Tech,Blacksburg,Virginia,USA;Graduate Program in Translational Biology,Medicine,and Health,Virginia Tech,Roanoke,Virginia,USA.;School of Neuroscience,Virginia Tech,Blacksburg,Virginia,USA)

机构地区：[1]Fralin Biomedical Research Institute at Virginia Tech Carilion,Roanoke,Virginia,USA. [2]Department of Biological Sciences,Virginia Tech,Blacksburg,Virginia,USA. [3]Graduate Program in Translational Biology,Medicine,and Health,Virginia Tech,Roanoke,Virginia,USA. [4]School of Neuroscience,Virginia Tech,Blacksburg,Virginia,USA. [5]不详

出　　处：《神经损伤与功能重建》2021年第11期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：已知在成年大脑中多种细胞类型会产生调节血脑屏障(BBB)特性的因子,包括星形胶质细胞。然而,最近的几项研究对成熟星形胶质细胞在BBB中的作用提出了质疑。我们使用他莫昔芬诱导的星形胶质细胞消融小鼠模型,以确定星形胶质细胞在维持成年BBB中是否有有着非冗余和必要功能。在成年小鼠中,他莫昔芬诱导在2 h内导致星形胶质细胞稀疏的凋亡性死亡。早在星形胶质细胞消融出现时即可检测到小分子尸胺的渗漏和进入脑实质的大血浆蛋白纤维蛋白原等表明BBB损伤的迹象。在星形胶质细胞丢失区域内和邻近的血管,紧密连接蛋白zonula occludens-1的表达降低,而内皮葡萄糖转运蛋白1的表达不受干扰。尸胺渗漏持续数周,表明缺乏BBB的修复。这与消融的星形胶质细胞未被替换的发现一致。相邻的星形胶质细胞出现部分非增殖性胶质细胞增生,其特征是形态变化和STAT3的延迟磷酸化。这使泄漏入脑内的染料在消融1月后仍局限于缺乏星形胶质细胞覆盖的血管表面区域。总之,星形胶质细胞是维持成年大脑BBB完整性所必需的。其他细胞类型(如周细胞)分泌的BBB调节因子不足以补偿星形胶质细胞的缺失的影响。In the adult brain,multiple cell types are known to produce factors that regulate blood-brain barrier(BBB)properties,including astrocytes.Yet several recent studies disputed a role for mature astrocytes at the BBB.To determine if astrocytes contribute a nonredundant and necessary function in maintaining the adult BBB,we used a mouse model of tamoxifen-inducible astrocyte ablation.In adult mice,tamoxifen induction caused sparse apoptot-ic astrocyte cell death within 2 hr.Indicative of BBB damage,leakage of the small molecule Cadaverine,and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astro-cyte ablation was present.Vessels within and close to regions of astrocyte loss had lower expression of the tight junc-tion protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed.Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair.This is consistent with the finding that ablated astrocytes were not replaced.Adjacent astrocytes responded with partial nonproliferative astrogliosis,characterized by morphological changes and delayed phosphorylation of STAT3,which restricted dye leakage to the brain and ves-sel surface areas lacking coverage by astrocytes 1 month after ablation.In conclusion,astrocytes are necessary to maintain BBB integrity in the adult brain.BBB-regulating factors secreted by other cell types,such as pericytes,are not sufficient to compensate for astrocyte loss.

关 键 词：星形胶质细胞增生 接触抑制 胶质疤痕 胶质血管单位 紧密连接 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]