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

对空间认知的影响：遵循我们传统的缺血状态10min单一4-VO在闭塞后24小时对大鼠空间认知造成明显的破坏，我们也有报道称这种破坏逐渐恢复，重复试验。重度脑缺血时间延长至20 min后，空间认知功能明显受损，但仍有大量大鼠缺血不能正常进行或死亡。虽然3、5min反复缺血对大鼠空间认知功能的破坏极轻微，大部分大鼠均能存活，但10min反复缺血即使在7天内也会造成严重的空间认知功能破坏，这取决于次数，间隔1小时缺血2、3 -10min的大鼠存活率分别为90%、75%。对脑细胞的影响：为了研究反复缺血对海马背侧的影响，在存活7天时，制备大鼠脑，用血色素染色，光镜下观察，测定海马CA1亚区神经元密度（/mm）。反复缺血与单次缺血相比，不同次数的反复缺血使细胞萎缩，细胞损失明显，胶质细胞增殖明显。对乙酰胆碱释放的影响：众所周知，额叶皮质（FC）和海马背侧（DH）与记忆和学习密切相关，我们测定了FC和DH对乙酰胆碱释放的影响。FC单次缺血10min时，预值瞬时升高约3倍，间隔1小时缺血2次或3次10min时，也可观察到相同的变化。3 ~ 10min缺血间隔1 h，第3 ~ 10min缺血时DH中乙酰胆碱释放量无短暂性增加。另一方面，我们观察到在24小时和7天后，根据缺血的重复次数，FC和DH的乙酰胆碱释放明显减少。药物作用：我们的数据显示，MK-801 （NMDA拮抗剂）、L-thero-DOPS （NA相对药物）和THA （ACh相对药物）在缺血7天时增强了重复缺血引起的空间认知破坏。葡萄糖的运动：有研究认为，局部脑区能量代谢紊乱可引起脑神经元死亡。我们提出了一种新的方法——体内生物传感器，来研究缺血时早期脑能量代谢的变化。实时生物传感显示，缺血后葡萄糖水平立即下降，缺血期间葡萄糖水平基本保持不变，再灌注15 min后逐渐恢复，50 min内恢复到缺血前水平。少

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