Disruption of spatial cognition following repeated-ischemia in radial arm maze and improvemental effect of radical scavengers

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Effects on the spatial cognition : Following our traditional ischemic condition ; 10 min single 4-VO induced obviously disruption of spatial cognition in rat at 24 hours after occlusion and we've also been reported that this disruption was gradually recovered, as repeat the trial. Prolong the ischemic period to 20 min for the severer insult, the disruption of spatial congnition was getting clearly, but many rats couldn't carry out the trial or died during ischemia.Although 3 or 5min repeated ischemia induced extremely slight disruption of spatial congnition and most of the rats can alive, 10 min repeated ischemia produced severe disruption of spatial congnition even in 7 days, depending on the number of times, and the survival rate is 90 %, 75% in two-, three-10min ischemia at 1 hour interval, respectively.Effects on the brain cell : In order to examine the effects of repeated ischemia on Dorsal hppocampus, at the 7 days of survival, the rat's brain were prepared and stained with hemat … More oxylin-cosin and examined with a light microscope and the neuronal density (/mm) of the CA1 subfield of the hippocampus was determined. As compared with single periods of ischemia, repeated ischemia produced shrinkage of cell, markedly cell loss and proliferation of glia cell, depending on repeated numeber of ischemia.Effects on the ACh release : Since Frontal Cortex (FC) and Dorsal Hippocampus (DH) are well known to closely related to memory and learning, We determined the change of ACh release from FC and DH.There's about 3-times of pre value increased transiently during 10 min single ischemia in FC and we can observed the same changes in two- or three-10min ischemia at 1 hour interval. However, There's no transient increase of ACh release from DH during the 3rd 10 min ischemia in three-10min ischemia at 1 hour interval. On the other hands, we observed the markdely decrease of ACh release from both FC and DH after either 24 hours and 7 days, depending on repeated numeber of ischemia. Effects of drug : Our data showed that MK-801 (the NMDA antagonist), L-thero-DOPS (the NA relative drug) and THA (the ACh relative drug) enhance the repeated ischemia -induced disruption of spatial cognition at the 7 days of ischemia. Movement of glucose : It has been suggested that a disturbance of energy metabolism in local cerebral region pulls the trriger the cerebral neuronal death. We worked out the new method, in vivo biosensor, to investigate to how the cerebral energy metabolism get change from carly at the time point of ischemia. The real time biosensoring shows that the glucose level decreased right after ischemia, kept the almost same level during the ischmia, gradually recoverd with reperfusion maximam by 15 min, and come back to the pre-value within 50 min. Less