Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier
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Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier. / Lou, Nanhong; Takano, Takahiro; Pei, Yong; Xavier, Anna L.; Goldman, Steven A.; Nedergaard, Maiken.
In: National Academy of Sciences. Proceedings, Vol. 113, No. 4, 26.01.2016, p. 1074-1079.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier
AU - Lou, Nanhong
AU - Takano, Takahiro
AU - Pei, Yong
AU - Xavier, Anna L.
AU - Goldman, Steven A.
AU - Nedergaard, Maiken
PY - 2016/1/26
Y1 - 2016/1/26
N2 - 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 juxtavascular microglial 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.
AB - 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 juxtavascular microglial 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.
KW - Animals
KW - Blood-Brain Barrier
KW - Cell Movement
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Microglia
KW - Platelet Aggregation Inhibitors
KW - Receptors, Purinergic P2Y12
KW - Ticlopidine
KW - Journal Article
KW - Research Support, N.I.H., Extramural
U2 - 10.1073/pnas.1520398113
DO - 10.1073/pnas.1520398113
M3 - Journal article
C2 - 26755608
VL - 113
SP - 1074
EP - 1079
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 4
ER -
ID: 164971996