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

激活的小胶质细胞和扩散的抑郁症对受损中枢神经系统组织的影响

• 批准号: 09470289
• 负责人: YAMAURA Akira
• 金额: $ 8.45万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470289/
• 关键词: Experimental brain injury; neuronal cell death; microglia; FK506; spreading depression; Morris water maze; neurobehavior; 頭部外傷; fluid-percussion injury; 軸索損傷; rotarod; beam balanca; beam walking

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.

我们的改良液压冲击损伤装置恢复，使大鼠可再生的创伤性脑损伤。在该模型中，丘脑中的小胶质细胞活化和神经元细胞损失被很好地再现。没有宏观脑损失的轻度损伤动物具有最小的运动障碍，这仅在梁平衡任务中被注意到。伤后1小时，静息状态的小胶质细胞被激活，出现形态学改变。双侧海马“丛状”小胶质细胞增多。在同侧海马CA 1、CA 4及双侧齿状回可见“变形样”小胶质细胞。“杆状”小胶质细胞常沿着HRP阳性神经元的树突分布。6小时后，“丛状型”小胶质细胞恢复为静息型。在脑外伤亚急性期（1 ~ 7天），观察小胶质细胞和星形胶质细胞的反应及轴索损伤。丘脑的轴突损伤似乎与小胶质细胞的活化密切相关，在损伤后7天和14天，单用FK 506治疗的大鼠中存活的神经元细胞的数量显著大于溶剂治疗的大鼠。然而，每日一次FK 506给药大鼠的数量与溶媒给药大鼠的数量无差异。FK 506每日给药大鼠中OX 42阳性小胶质细胞的数量显著少于溶剂给药大鼠。在大鼠创伤性脑损伤后立即给予FK 506似乎限制了LD核中神经元细胞的死亡。

项目成果

Higuchi Y.Murai H.Sato M.Yamaura A.: "Effects of FK506 on neuronal cell death after lateral fluid percussion brain injury in rats"International Conference Recent Advances in NEUROTRAUMATOLOGY. 163-167 (1999)

Higuchi Y.Murai H.Sato M.Yamaura A.：“FK506 对大鼠侧向液体冲击脑损伤后神经元细胞死亡的影响”国际会议神经创伤学最新进展。

Higuchi Y. Murai H. Sato M. Yamaura A.: "Effects of FK506 on neuronal cell death after lateral fluid percussion brain injury in rats."International Conference on Recent Advances in NEUROTRAUMATOLOGY. 163-167 (1999)

Higuchi Y. Murai H. Sato M. Yamaura A.：“FK506 对大鼠侧向液体冲击脑损伤后神经元细胞死亡的影响。”神经创伤学最新进展国际会议。

Higuchi Y., Murai H., Sato M., Yamaura A.: "Effects of FK506 on neuronal cell death after lateral fluid percussion brain injury in rats"International Conference on Recent Advances in NEUROTRAUMATOLOGY. 163-167 (1999)

Higuchi Y.、Murai H.、Sato M.、Yamaura A.：“FK506 对大鼠侧向液体冲击脑损伤后神经元细胞死亡的影响”神经创伤学最新进展国际会议。