Association of Pericyte Loss With Microthrombosis After Subarachnoid Hemorrhage in ApoE-Deficient Mice.
Association of Pericyte Loss With Microthrombosis After Subarachnoid Hemorrhage in ApoE-Deficient Mice.
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ApoE 缺陷小鼠蛛网膜下腔出血后周细胞丢失与微血栓形成的关系。
DOI：
10.3389/fneur.2021.726520
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发表时间：
2021
影响因子：
3.4
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Pang J;Wu Y;Peng J;Yang P;Chen L;Jiang Y
背景：微血栓的发生不仅与SAH后迟发性脑缺血（DCI）有关，而且与SAH后早期脑损伤（EBI）有关。然而，其内在机制尚未完全研究。本研究旨在探讨ApoE基因缺陷小鼠SAH后EBI期微血栓形成的机制。方法：采用载脂蛋白E（ApoE）缺陷小鼠和野生型（WT）小鼠血管内穿孔法建立实验性SAH模型。采用神经行为学、分子生物学和组织病理学方法评估周细胞丢失、神经行为学表现和微血栓形成之间的关系。结果：WT小鼠SAH后微血栓数量明显增多，48 h达高峰。微血栓形成的增加与微循环有效灌注面积的减少和EBI的严重程度有关。ApoE缺陷小鼠在SAH后48 h表现出比WT小鼠更广泛的微血栓形成，从而与更大的神经行为缺陷相关。免疫组化染色显示，微血栓主要位于微血管周细胞覆盖的情况下。从机制上讲，ApoE缺乏导致比WT小鼠中观察到的更广泛的CypA-NF-κB-MMP-9途径活化，从而导致更多的N-钙粘蛋白降解，随后更多的周细胞损失。此后，促进微血管中微血栓形成的主要粘附分子P-选择素在WT小鼠中显著增加，并且在ApoE缺陷小鼠中增加到更大程度。结论：这些数据表明，周细胞丢失通过促进微血栓形成与SAH后EBI相关。靶向ApoE以减少微血栓形成的疗法可能是SAH治疗的有希望的策略。
Background: The occurrence of microthrombosis contributes to not only delayed cerebral ischemia (DCI), but also early brain injury (EBI) after SAH. However, the underlying mechanism is not completely investigated. In the current study, we explored the underlying mechanism of microthrombosis in EBI stage after SAH in ApoE-deficient mice. Methods: Experimental SAH was established by endovascular perforation in apolipoprotein E (ApoE)-deficient mice and wild type (WT) mice. Neurobehavioral, molecular biological and histopathological methods were used to assess the relationship between pericytes loss, neurobehavioral performance, and microthrombosis. Results: We found that the number of microthrombi was significantly increased and peaked 48 h after SAH in WT mice. The increased microthrombosis was related to the decreased effective microcirculation perfusion area and EBI severity. ApoE-deficient mice showed more extensive microthrombosis than that of WT mice 48 h after SAH, which was thereby associated with greater neurobehavioral deficits. Immunohistochemical staining showed that microthrombi were predominantly located in microvessels where pericytes coverage was absent. Mechanistically, ApoE deficiency caused more extensive CypA-NF-κB-MMP-9 pathway activation than that observed in WT mice, which thereby led to more degradation of N-cadherin, and subsequently more pericytes loss. Thereafter, the major adhesion molecule that promoting microthrombi formation in microvessels, P-selectin, was considerably increased in WT mice and increased to a greater extent in the ApoE-deficient mice. Conclusion: Taken together, these data suggest that pericytes loss is associated with EBI after SAH through promoting microthrombosis. Therapies that target ApoE to reduce microthrombosis may be a promising strategy for SAH treatment.
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影响因子：
9.8
作者：
Rowland, M. J.;Hadjipavlou, G.;Pattinson, K. T. S.
通讯作者：
Pattinson, K. T. S.
影响因子：
15.1
作者：
Cui J;Chen S;Zhang C;Meng F;Wu W;Hu R;Hadass O;Lehmidi T;Blair GJ;Lee M;Chang M;Mobashery S;Sun GY;Gu Z
通讯作者：
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影响因子：
4.2
作者：
Cao, Fang;Jiang, Yong;Sun, Xiaochuan
通讯作者：
Sun, Xiaochuan
影响因子：
3.4
作者：
Schutzman, Linda M.;Rigor, Robert R.;Brown, Ian E.
通讯作者：
Brown, Ian E.
影响因子：
4.1
作者：
Nagahama, Yasunori;Allan, Lauren;Hasan, David
通讯作者：
Hasan, David