Clonidine preconditioning alleviated focal cerebral ischemic insult in rats via up-regulating p-NMDAR1 and down-regulating NMDAR2A / p-NMDAR2B.
A brain ischemia rat model was established by middle cerebral artery occlusion (MCAO) for 2h and reperfusion for 4h to investigate the underlying mechanism of the neuroprotection action of clonidine, a classical alpha-2 adrenergic agonist, on cerebral ischemia. Clonidine and yohimbine were intraperitoneally given to the rats each day for a week before ischemia. Neurological deficits evaluations were carried out at 6h after operation. TTC staining method was used to measure the volume of brain infarction. Expression levels of NMDAR1, NMDAR2A, NMDAR2B were assayed by western blotting. Our data demonstrated that clonidine pretreatment significantly improved the neurological deficit scores and reduced the brain infarct volumes of the rats. Furthermore, protein expression level of p-NMDAR2B in cortex was significantly up-regulated whereas that of p-NMDAR1 was decreased when compared with the sham-operated rats. Remarkably, clonidine treatment led to significant down-regulation of p-NMDAR2B and NMDAR2A in addition to enhancement of the expression level of p-NMDAR1 in cortex. This is the first report illustrating the neuroprotective role of clonidine may be mediated through modulation of the expression levels of p-NMDAR2B, NMDAR2A and p-NMDAR1 during cerebral ischemia.
Medical School of China Three Gorges University, Yichang 443002, PR China.
Li
L
Yanli
The First Renmin Hospital of Yichang City, Yichang 443002, PR China.
Zhang
Z
Xizhou
The First People's Hospital of Foshan City, Foshan 528000, PR China.
Wang
W
Yan
Medical School of China Three Gorges University, Yichang 443002, PR China.
Zhao
Z
Bo
The First Renmin Hospital of Yichang City, Yichang 443002, PR China.
Zha
Z
Yunhong
Medical School of China Three Gorges University, Yichang 443002, PR China.
Li
L
Zicheng
Medical School of China Three Gorges University, Yichang 443002, PR China.
Yu
Y
Lingling
Tianyou Affiliated Hospital,Wuhan University of Science and Technology, Wuhan 430070, PR China.
Yan
Y
Lingling
Wuhan Medtek, Biomedical Technology Co., LTD, Wuhan 430064, PR China.
Chen
C
Zhangao
School of Biomedical Engineering of Hubei University of Science and Technology, Xianning 437100, PR China.
Zheng
Z
Min
Medical School of China Three Gorges University, Yichang 443002, PR China. Electronic address: hezhi2003@163.com.
He
H
Zhi
D000818:Animals; D001929:Brain Edema / Q000150:complications; D003000:Clonidine / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D019194:Ischemic Preconditioning; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D003000:Clonidine; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
Cerebral ischemia; Clonidine; NMDAR1; NMDAR2A; NMDAR2B