MEK/ERK- and calcineurin/NFAT-mediated mechanism of cerebral hyperemia and brain injury following NMDA receptor activation
MEK/ERK- and calcineurin/NFAT-mediated mechanism of cerebral hyperemia and brain injury following NMDA receptor activation
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DOI：
10.1016/j.bbrc.2017.05.043
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发表时间：
2017-06-24
影响因子：
3.1
通讯作者：
Ishii, Kunio
中科院分区：
文献类型：
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作者：
Kurauchi, Yuki;Kinoshita, Rintaro;Ishii, Kunio
N-甲基-D-天冬氨酸(NMDA)受体激活可增加局部脑血流量(RCBF)并诱导神经元损伤，但这些过程之间的相似性尚不清楚。在这项研究中，通过在活体内测量rCBF，我们确定了脑充血和脑损伤之间的明显相关性。NMDA受体激活引起的脑损伤是rCBF增加的结果，而有丝分裂原激活的蛋白激酶或钙调神经磷酸酶的抑制剂可减轻这种损伤。此外，NMDA还可诱导神经元细胞外信号调节激酶(ERK)的磷酸化和活化T细胞核因子(NFAT)的核转位。因此，MEK/ERK和Calcineurin/NFAT介导的神经血管偶联机制是神经血管疾病的病理生理学基础。(C)2017 Elsevier Inc.保留所有权利。
N-methyl-D-aspartate (NMDA) receptor activation increases regional cerebral blood flow (rCBF) and induces neuronal injury, but similarities between these processes are poorly understood. In this study, by measuring rCBF in vivo, we identified a clear correlation between cerebral hyperemia and brain injury. NMDA receptor activation induced brain injury as a result of rCBF increase, which was attenuated by an inhibitor of mitogen-activated protein kinase or calcineurin. Moreover, NMDA induced phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear translocation of nuclear factor of activated T cell (NFAT) in neurons. Therefore, a MEK/ERK- and calcineurin/NFAT-mediated mechanism of neurovascular coupling underlies the pathophysiology of neurovascular disorders. (C) 2017 Elsevier Inc. All rights reserved.