Effects of activated microglia and spreading depression on the injured CNS tissue

采用改进的液体冲击损伤装置修复大鼠创伤性脑损伤。在这个模型中，丘脑小胶质细胞的激活和神经元细胞的损失得到了很好的再现，轻度损伤的动物没有宏观的脑损伤，只有在波束平衡任务中才会注意到运动障碍。然而，记忆障碍被清楚地证明。损伤后1小时，静息小胶质细胞被激活，形态学改变。双侧海马的“丛型”小胶质细胞全部增加。同侧CA1、CA4及双侧齿状回可见“变形虫型”小胶质细胞。“杆状”小胶质细胞常见于HRP结合神经元的树突。6小时后，“浓密型”小胶质细胞恢复为静息型。然而，“变形虫型”小胶质细胞仍然存在于该部位。在颅脑损伤亚急性期（1 ~ 7 d）观察小胶质细胞、星形胶质细胞和轴突损伤的反应。丘脑轴突损伤似乎与激活的小胶质细胞密切相关。损伤后第7天和第14天，单个FK506处理大鼠的神经元细胞存活数量明显大于对照处理大鼠。然而，每日FK506处理大鼠的数量与车辆处理大鼠的数量没有差异。FK506每日给药大鼠的OX42阳性小胶质细胞数量明显少于载药大鼠。在创伤后立即给予FK506，似乎可以限制创伤性脑损伤大鼠LD核神经元细胞的死亡。

Our modified fluid-percussion injury device was restored to make reproducible traumatic brain injuries in rats. Microglial activation and neuronal cell loss in the thalamus was well reproduced in this modelMildly injured animals without macroscopic brain loss had minimal motor disturbance, which was only noted in the beam-balancing task. However, memory disturbance was clearly demonstrated.At 1 hour following injury, resting microglia were activated to show morphological changes. "Bushy type" microglia increased all over the bilateral hippocampus. "Amoeboid type" microglia were noted in the ipsilateral CA1, CA4 and bilateral dentate gyrus. "Rod type" microglia were often found along the dendrites of HRP incorporated neurons. At 6 hours, "bushy type" microglia were returned to the resting type. However, "amoeboid type" microglia were still remained in the site.In the subacute stage (1 to 7 days) of traumatic brain injury, reactions of microglia and astrocyte, and axonal injuries were studied. Axonal injuries in the thalamus were seemed to be closely associated with the activated microglia.The number of survived neuronal cells in the single FK506 treated rats was significantly larger than the vehicle treated rats at 7 and 14 days following injury. However, the number in daily FK506 treated rats did not differ from that in the vehicle treated rats. The number of OX42 positive microglia in daily FK506 treated rats was significantly fewer than that in vehicle treated rats. FK506, when administered immediately after the injury, appeared to limit neuronal cell death in LD nucleus in traumatic brain injury in ratsSpreading depression studies were started using controlled cortical impact injury model.