Study On The Relationship Between Spreading Depression And Damage In Remote Encephalic Region After Focal Cerebral Ischemia

【Objective】Spreading depression (SD) is a pathophysiological phenomenon observed in the CNS with characteristic ionic, metabolic and hemodynamic changes. SD plays an important role in some clinical disorders including migraine, cerebrovascular diseases, head injury and transient global amnesia. In the present study, we investigated the construction of the electrophysiological technique platform of SD in vivo, modified the recording method of SD, and applied it to the electrophysiological research of the region remote from ischemia area of focal cerebral ischemia.【Materials and Methods】We elicited SD by high concentration potassium chloride solution, photochemical thrombotic focal cerebral ischemia and middle cerebral artery occlusion (MCAO) cerebral ischemia, and we inhibited SD by applying MK-801 previously. We recorded DC potential with Ag/AgCl electrode by this method. Additionally, the method was improved and applied to electrophysiological research in hippocampus of MCAO model.【Results】In potassium chloride group there was no visible DC potential change before the applying of potassium chloride solution on the right cortex of parietal lobe in all the animals; during the 60 min following the applying of potassium chloride, repeated huge negative DC potential shifts (SD waves) were recorded at the ipsilateral occipital cortex in all the animals. In the photochemical thrombotic cerebral ischemia group, there was no visible DC potential change before the photochemical thrombotic cerebral ischemia of the right cortex of parietal lobe in all the animals; during the 60 min following ischemia, repeated huge negative DC potential shifts (SD waves) were recorded at the ipsilateral occipital cortex in all the animals of this group. In the MCAO group DC potential was recorded in occipital cortex and hippocampus respectively in different animals. No visible DC potential change was recorded before the MCAO cerebral ischemia model, and during the 60 min of the ischemia, repeated huge negative DC potential shifts (SD waves) were recorded. No visible DC potential change was recorded during the corresponding time course in all the animals of control group.【Conclusion】In this study we established the electrophysiological technique platform of SD in vivo. We recorded SD waves induced by high concentration potassium chloride solution and focal cerebral ischemia. After modifying the recording electrode we recorded SD waves in hippocampus following MCAO by this method. 【Objective】Hippocampal delayed neuronal death was observed after middle cerebral artery occlusion (MCAO). The mechanics of this remote damage has rarely been reported. Spreading depression (SD) is a pathophysiological phenomenon which plays an important role in various clinical disorders. The aim of this part is to explore the relationship between SD which was induced by focal cerebral ischemia and the DND in ipsilateral hippocampus after MCAO.【Materials and Methods】A rat model of MCAO was made by the intraluminal suture technique. The SD waves were recorded by electrophysiological method with the technique platform constructed in part one. Delayed neuronal death in the hippocampus was observed by Nissl's staining and TUNEL labeling.【Results】With no inhibitor of SD, DND was detected in 39% of the animals in hippocampal CA1 region 3 days after MCAO. Applying MK-801, the inhibitor of SD, DND only appeared in 10% of the animals in hippocampal CA1 region 3 days after MCAO.【Conclusion】Inhibition of SD significantly reduced the probability of hippocampal DND after MCAO. SD might have relation to DND in hippocampus after middle cerebral artery occlusion. 【Objective】Apply the in vivo microdialysis sampling technique to explore the dynamic changes of the extracellular amino acids concentrations in ischemia region and in remote region during focal cerebral ischemia-reperfusion. To explore t he effect of ischemia induced spreading depression on the extracellular concentrations of amino acids in rat hippocampus after middle cerebral artery occlusion.【Materials and Methods】Construct the in vivo microdialysis sampling technique platform and applying to the research of dynamic changes of the extracellular amino acids concentrations in different encephalic regions during focal cerebral ischemia-reperfusion. A rat model of middle cerebral artery occlusion was used to produce focal brain ischemia-reperfusion with ischemia core and remote region. In vivo brain microdialysis sampling and high performance capillary electrophoresis detecting were applied to monitor the dynamic changes of extracellular concentrations of amino acids in different encephalic region. Observe the effect of spreading depression induced by ischemia on the extracellular concentrations of amino acids in the hippocampus by in vivo microdialysis sampling and high performance capillary electrophoresis detecting.【Results】The extracellular concentrations of amino acids in ischemia region (striatum) increased at 20 min after middle cerebral artery occlusion, and maintained at high level in the 60 min of ischemia and following 60 min of reperfusion. The extracellular concentrations of amino acids in remote region (hippocampus) also increased at 20 min after middle cerebral artery occlusion, and the dynamic change had two characteristic peaks during ischemia period and reperfusion period. The extracellular concentrations of amino acids in striatum and hippocampus in sham-operated group had no significant change at correspondence time point. The extracellular concentrations of amino acids in hippocampal CA1 region increased following middle cerebral artery occlusion, and were attenuated by the inhibitor of spreading depression.【Conclusion】As focal brain ischemia-reperfusion caused damage in ischemia region, corresponding physiopathologic lesion occurred in remote region. Spreading depression might have relation to remote region lesion in hippocampus after middle cerebral artery occlusion.