Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier

被引：243

作者：

Lou, Nanhong ^{[1
]}

Takano, Takahiro ^{[1
]}

Pei, Yong ^{[1
]}

Xavier, Anna L. ^{[1
]}

Goldman, Steven A. ^{[1
,2
]}

Nedergaard, Maiken ^{[1
,2
]}

机构：

[1] Univ Rochester, Sch Med, Ctr Translat Neuromed, Rochester, NY 14642 USA

[2] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Translat Neuromed, DK-2200 Copenhagen, Denmark

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2016年 / 113卷 / 04期

基金：

美国国家卫生研究院;

关键词：

purinergic receptors; microglia; blood-brain barrier; stroke; clopidogrel; PLATELET ADP-RECEPTOR; ACTIVE METABOLITE; P2Y(12) RECEPTOR; CLOPIDOGREL; STROKE; ASPIRIN; CELLS; LASER; IDENTIFICATION; ACTIVATION;

D O I：

10.1073/pnas.1520398113

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Microglia are integral functional elements of the central nervous system, but the contribution of these cells to the structural integrity of the neurovascular unit has not hitherto been assessed. We show here that following blood-brain barrier (BBB) breakdown, P2RY12 (purinergic receptor P2Y, G-protein coupled, 12)-mediated chemotaxis of microglia processes is required for the rapid closure of the BBB. Mice treated with the P2RY12 inhibitor clopidogrel, as well as those in which P2RY12 was genetically ablated, exhibited significantly diminished movement of juxtavascularmicroglial processes and failed to close laser-induced openings of the BBB. Thus, microglial cells play a previously unrecognized protective role in the maintenance of BBB integrity following cerebrovascular damage. Because clopidogrel antagonizes the platelet P2Y12 receptor, it is widely prescribed for patients with coronary artery and cerebrovascular disease. As such, these observations suggest the need for caution in the postincident continuation of P2RY12-targeted platelet inhibition.

引用

页码：1074 / 1079

页数：6

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