PATHOPHYSIOLOGY AND TREATMENT OF STRIATONIGRAL ISCHEMIC INJURY

纹状体黑质缺血性损伤的病理生理学和治疗

• 批准号: 05671173
• 负责人: NAGAHIRO Shinjl
• 金额: $ 1.34万
• 依托单位: KUMAMOTO UNIVERSITY MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671173/
• 关键词: TRANSIENT CEREBRAL ISCHEMIA; STRIATUM; SUBSTANTIA NIGRA; MAGNETIC RESONANCE IMAGING; APOMORPHINE; MICROGLIA; IMMUNOHISTOCHEMISTRY; TRANSPLANTATION; カルレチニン; 燐酸化チロシン; ミクログリア; 移植; 再生; 免疫組織化学; カルシウム結合蛋白; 一過性虚所脳虚血; 脳血管透過性; アポモルフィン; カルシニューリン

Behavioral, magnetic resonance imaging and histological studies were performed on the striatonigral system of rats with unilateral reversible middle cerebral occlusion, and following results were obtained.(1) The rats subjected to 15 to 120 minutes ischemia exhibited the ipsiversive rotational behavior elicited by systemic administration of dopamine receptor agonist apomorphine.(2) magnetic resonance imaging study showed that T2 high-signal-intensity aresa appeared earlier in the ipsilateral striatum and cortex and the size increased with the duration of ischemia. Disruption of the blood-cerebrospinal fluid barrier following transient ischemia was demonstrated by MR imaging using Gd-DTPA enhancement.(3) Histologically, the ipsilateral striatum of the rats showed a subdivisional ischemic injury. The striatal lesions having a cell type-specific injury were located in the dorsolateral portion of the rostral striatum. There was also a marked depletion of striatonigral afferents in the lateral portion of the substantia nigra pars reticulata. Activation of the microglia was noted in the ipsilateral cortex and the substantia nigra following ischemia.(4) Immunohistochemical study in the rat with striatal ischemic lesion followed by intrastriatal grafts derived from fetal striatal peimordia demonstrated that the striatopallidal pathway was reformend by striatal projection neurons of the transplants.

对单侧可逆性大脑中动脉阻塞大鼠的纹状体黑质系统进行了行为学、磁共振成像和组织学研究。(1)缺血15 - 120分钟的大鼠表现出由多巴胺受体激动剂阿扑吗啡引起的自发旋转行为。(2)磁共振成像显示，缺血侧纹状体和皮质T2高信号区出现较早，且随缺血时间延长而增大。短暂性脑缺血后血-脑脊液屏障的破坏通过使用Gd-DTPA增强的MR成像证实。(3)组织学上，大鼠的同侧纹状体表现为亚分区缺血性损伤。具有细胞类型特异性损伤的纹状体病变位于吻侧纹状体的背外侧部分。在黑质网状部的外侧部分，纹状体黑质传入神经也明显减少。在缺血后，在同侧皮质和黑质中观察到小胶质细胞的激活。(4)免疫组织化学研究表明，移植的纹状体投射神经元对纹状体的投射通路有一定的改善作用。

项目成果

Shinji Nagahiro: "Disruption of the blood-cerebrospinal fluid barrier by transient cerebral ischemia" Braian Research. 633. 305-311 (1994)

Shinji Nagahiro：“短暂性脑缺血破坏血脑脊液屏障”Braian Research。

Kazumichi Yamada: "Striatal cells containing the Ca2+-binding protein calretinin (protein 10) in ischemia-induced neuronal injury." Acta Neuropathol. 89. 172-177 (1995)

Kazumichi Yamada：“在缺血引起的神经元损伤中，纹状体细胞含有 Ca2 结合蛋白钙结合蛋白（蛋白 10）。”

Kazumichi Yamada: "Elevated immunoreactivity for glutamic acid decarboxylase in the rat cerebral cortex following transient middle cerebral artery occlusion." Acta Neuropathol.,. 88. 55-59 (1994)

Kazumichi Yamada：“短暂大脑中动脉闭塞后，大鼠大脑皮层中谷氨酸脱羧酶的免疫反应性升高。”

Kojiro Korematsu: "Changes of immunoreactivity for synaptophysin ( 'protein p38' ) following a transient cerebral ischemia in the rat striatum." Brain Research. 616. 320-324 (1993)

Kojiro Korematsu：“大鼠纹状体短暂性脑缺血后突触素（‘蛋白质 p38’）免疫反应性的变化。”

Shinji Nagahiro: "Disruption of the blood-cerebrospinal fluid barrier by transient cerebral ischemia" Brain Research. 633. 305-311 (1994)

Shinji Nagahiro：“短暂性脑缺血破坏血脑脊液屏障”脑研究。