Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age.
Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age.
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DOI：
10.1038/s41467-022-29475-2
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发表时间：
2022-04-04
影响因子：
16.6
通讯作者：
Sontheimer H
中科院分区：
文献类型：
--
作者：
Mills WA 3rd;Woo AM;Jiang S;Martin J;Surendran D;Bergstresser M;Kimbrough IF;Eyo UB;Sofroniew MV;Sontheimer H
星形胶质细胞延伸包围脉管系统的末端足，并且这种关联的破坏可能发生在疾病中与血脑屏障（BBB）完整性的破坏相一致。在这里，我们调查，如果局灶性消融星形胶质细胞是足以破坏小鼠血脑屏障。有针对性的双光子化学凋亡消融星形胶质细胞诱导的可塑性反应，从而周围的星形胶质细胞扩展过程，以覆盖血管空缺。在年轻动物中，替换过程发生在端足回缩之前，但在老年动物中延迟。刺激替代星形胶质细胞导致毛细血管前小动脉收缩，表明替代星形胶质细胞是功能性的。pSTAT3的药理学抑制以及pSTAT3的星形胶质细胞特异性缺失减少了消融后的星形胶质细胞替代，而不干扰BBB完整性。在中风模型中，由于再灌注，星形胶质细胞死亡后发生类似的终足替换。总之，这些研究揭示了星形胶质细胞通过替代附近细胞来维持脑血管覆盖的能力。血脑屏障的破坏可能发生在几种疾病中。在这里，作者表明，星形胶质细胞的靶向消融导致附近细胞的可塑性机制，以保持脑血管覆盖，但这种机制在老年动物中受损。
Astrocytes extend endfeet that enwrap the vasculature, and disruptions to this association which may occur in disease coincide with breaches in blood-brain barrier (BBB) integrity. Here we investigate if focal ablation of astrocytes is sufficient to disrupt the BBB in mice. Targeted two-photon chemical apoptotic ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes to cover vascular vacancies. In young animals, replacement processes occur in advance of endfoot retraction, but this is delayed in aged animals. Stimulation of replacement astrocytes results in constriction of pre-capillary arterioles, suggesting that replacement astrocytes are functional. Pharmacological inhibition of pSTAT3, as well as astrocyte specific deletion of pSTAT3, reduces astrocyte replacement post-ablation, without perturbations to BBB integrity. Similar endfoot replacement occurs following astrocyte cell death due to reperfusion in a stroke model. Together, these studies uncover the ability of astrocytes to maintain cerebrovascular coverage via substitution from nearby cells. Disruption of the blood brain barrier can occur in several diseases. Here the authors show that targeted ablation of astrocytes results in a plasticity mechanism in nearby cells to maintain cerebrovascular coverage, but that this mechanism is impaired in older animals.
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DOI：
10.1093/brain/awv328
发表时间：
2016-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Chen A;Akinyemi RO;Hase Y;Firbank MJ;Ndung'u MN;Foster V;Craggs LJ;Washida K;Okamoto Y;Thomas AJ;Polvikoski TM;Allan LM;Oakley AE;O'Brien JT;Horsburgh K;Ihara M;Kalaria RN
通讯作者：
Kalaria RN
AG490通过抑制JAK2/STAT3介导的HMGB1在蛛网膜下腔出血中的调节来改善脑损伤。
影响因子：
2.7
作者：
An JY;Pang HG;Huang TQ;Song JN;Li DD;Zhao YL;Ma XD
通讯作者：
Ma XD
影响因子：
9.3
作者：
Early, Alexandria N.;Gorman, Amy A.;Morganti, Josh M.
通讯作者：
Morganti, Josh M.
影响因子：
6.3
作者：
Ezan, Pascal;Andre, Pascal;Cohen-Salmon, Martine
通讯作者：
Cohen-Salmon, Martine
影响因子：
13.6
作者：
Damisah, Eyiyemisi C.;Hill, Robert A.;Grutzendler, Jaime
通讯作者：
Grutzendler, Jaime