Neuroprotective effects of cromakalim on cerebral ischemia-reperfusion injury in rats Correlation with hippocampal metabotropic glutamate receptor 1 alpha and glutamate transporter 1

被引:4
作者
Wang, Shilei [1 ]
Liu, Junchao [1 ]
Chang, Qingxian [1 ]
Li, Yu [1 ]
Jiang, Yan [1 ]
Wang, Shiduan [1 ]
机构
[1] Qingdao Univ, Coll Med, Affiliated Hosp, Dept Anesthesiol, Qingdao 266003, Shandong, Peoples R China
关键词
cerebral ischemia-reperfusion; cromakalim; glutamate receptor 1 alpha; glutamate transporter 1; SENSITIVE POTASSIUM CHANNEL; ARTERY OCCLUSION; GLUTAMATE; ACTIVATION; APOPTOSIS;
D O I
10.3969/j.issn.1673-5374.2010.09.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
BACKGROUND: Studies have reported that potassium channel openers exhibit a protective effect on cerebral ischemia-reperfusion injury and inhibit glutamate excitotoxicity in rats However, the effects of the glutamate receptor 1 alpha and glutamate transporter 1 remain poorly understood OBJECTIVE: To investigate the prophylactic use of the adenosine triphosphate-sensitive potassium channel opener cromakalim on neurological function and cerebral infarct size, as well as glutamate receptor 1 alpha and glutamate transporter 1 expression, in rats with cerebral ischemia-reperfusion injury, and to explore action mechanisms underlying reduced glutamate excitotoxicity and neuroprotection in rats DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment was performed at the Brain Institute, Qingdao University Medical College, Between July 2008 and April 2009 MATERIALS: Cromakalim was purchased from Sigma, USA, rabbit anti-glutamate receptor la polyclonal antibody was offered by Wuhan Boster, China, rabbit anti-glutamate transporter 1 polyclonal antibody was offered by Santa Cruz Biotechnology, USA METHODS: Sixty male, Wistar rats, aged 6 months, were randomly assigned to three groups (n = 20) sham-surgery, model, and cromakalim Intraluminal thread methods were used to establish middle cerebral artery occlusion in rats from the model and cromakalim groups Rats from the sham-surgery group were subjected to exposed common carotid artery, external carotid artery, and internal carotid artery, without occlusion Cromakalim (10 mg/kg) was administered 30 minutes prior to middle cerebral artery occlusion, but there was no intervention in the model and sham-surgery groups MAIN OUTCOME MEASURES: At 24 hours post-surgery, neurological behavioral functions were evaluated using Bederson's test, cerebral infarction volume was determined following tetrazolium chloride staining, and glutamate receptor 1 alpha and glutamate transporter 1 expressions were detected using immunohistochemistry RESULTS: Following cerebral ischemia-reperfusion injury, neurological behavioral malfunctions were obvious in all mice Focal cerebral infarction was detected in ischemic hemispheres, glutamate receptor 1 alpha expression increased, and glutamate transporter 1 expression decreased in the ischemic hemisphere (P < 0 05) Compared with the model group, neurological behavioral functions significantly improved, cerebral infarction volume was significantly reduced (P < 0 05), glutamate receptor la expression was significantly decreased, and glutamate transporter 1 expression was increased in the cromakalim group (P < 0 05) CONCLUSION: Improved neurological function and reduced cerebral infarction volume in rats through the preventive use of cromakalim could be related to decreased glutamate receptor 1 alpha expression and enhanced glutamate transporter 1 expression.
引用
收藏
页码:678 / 682
页数:5
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