The Effects Of Ketamine Preconditioned On The Cerebral Edema And AQP4 After The Transient Focal Cerebral Ischemia/Reperfusion In Rats

Objective:Brain edema is one of the serious pathological processes associated with many neurologic diseases,such as cerebral ischemia/reperfusion,brain tumor and traumatic brain injury.The increased intracranial pressure(ICP)and heniation are its sever sequels which potentially aggravate the neurologic outcome,even lead to death. Currently,there are no effective therapeutic drugs and measures for it.However,the findation of Aquaporins(AQPs) provides molecular basis for further understanding the regulation of water permeability across microvessels between blood and brain.AQPs are composed of a family of membrane proteins that facilitate the diffusion of water through the plasma membrane.And many subtypes of the water channels have been identified in mammals.Among these,AQP4 is the predominant subtype present in the brain and-mainly expressed at brain-blood and brain-CSF interfaces,including astrocyte endfeet that surround blood vessels,ependymal cells and microvascular endothelial cells.Several evidences suggest that AQP4 is involved in formation and resolution of brain edema.So the regulation for the expression of AQP4 in the brain may provide a new clue for the treatment of cerebral edema.Ketamine is extensively applied to intravenous anesthesia.Some experiments reveal that ketamine is endowed with neuroprotective activities,but others reveal not. Our experiment is made to explore the effect of ketamine pretreatment on cerebral edema in a rat model of brain ischemia reperfusion and assessed the involvement of AQP4.Methods:The healthy male Sprague-Dawley rats weighing 220～250gwere randomly divided into 3 groups:(Ⅰ) sham operation group(n=12);(Ⅱ) saline group(n=16);(Ⅲ) ketamine pretreatment group(n=16).The transient focal ischemia/reperfusion was induced by the middle carotid artery occlusion(MCAo).It was Carried out by introducing a silicone-coated monofilament nylon suture(diameter 0.28 mm)from the right external carotid artery(ECA) into the internal carotid artery(ICA) until its tip occluded the origin of the MCA.The filament was removed after 90 min to allow reperfusion.In groupⅢ,the rats were exposed to 5%ketamine intravenously for 30 min(1mg/kg/min) before suffered from cerebral ischemia.Similarly,the animals in groupⅡreceived saline at the same time and speed as the ones in groupⅢ.At the end of 24h reperfusion,the neurologic outcomes of the rats were scored,aad then were sacrificed after deeply anesthetized.The brains were quickly removed to assess cerebral edema by dry-wet method.The expression of AQP4 in the border of the infarct region was detected by western-blot.Results:Compared with the rats in groupⅠ,the neurologic function deficit,cerebral edema and AQP4 expression in the border of the ischemia zone were significant in groupⅡandⅢ.But ketamine pretreatment in groupⅢdid not improve neurologic outcome and cerebral edema significantly compared with groupⅡ.And ketamine appeared no obvious effect on AQP4 expression.Conclusion:ketamine preconditioned can not improve neurologic outcome and attenuate edema,this maybe is correlated with its no effect on AQP4 expression.