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 re...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 1α 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 1α 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 1α 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 1a 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 1α 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 1α 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 1α expression and enhanced glutamate transporter 1 expression.展开更多
Cromakalim,an adenosine triphosphate-sensitive potassium channel opener,exhibits protective effects on cerebral ischemia/reperfusion injury.However,there is controversy as to whether this effect is associated with aqu...Cromakalim,an adenosine triphosphate-sensitive potassium channel opener,exhibits protective effects on cerebral ischemia/reperfusion injury.However,there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability.Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury;it also reduced blood-brain barrier permeability,and alleviated brain edema,ultimately providing neuroprotection.展开更多
基金Shandong Provincial Science and Technology Plan Foundation
文摘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 1α 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 1α 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 1α 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 1a 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 1α 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 1α 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 1α expression and enhanced glutamate transporter 1 expression.
基金the Shandong Provincial Science and Technology Program,No. 2006GG202004
文摘Cromakalim,an adenosine triphosphate-sensitive potassium channel opener,exhibits protective effects on cerebral ischemia/reperfusion injury.However,there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability.Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury;it also reduced blood-brain barrier permeability,and alleviated brain edema,ultimately providing neuroprotection.
