1993 年度実績報告書

脳血管障害性パーキンソニズムの病態解析とその外科的治療法の開発

研究課題

研究課題/領域番号	05771027
研究機関	熊本大学
研究代表者	後藤恵熊本大学, 医学部, 助手 (50240916)
キーワード	striatum / substantia nigra / globus pallidus / transient ischemia / behavioral study / transplantation
研究概要	30分間の中大脳動脈閉塞による一過性脳虚血を施したラットでは、non-limbic striatumに一致する線条体背外側部に限局した遅発性神経細胞障害を呈することを確認した。この障害部位はcell-type specific injuryで特徴づけられ.中型有棘細胞の選択的脱落を呈していた。線条体-黒質系では黒質網状部の外側部にのみstriatonigral afferentsの消失をみた。従って、この動物モデルでは脳基底核神経回路網の中でmotor circuitが選択的に傷害されているものと考えている。また本動物モデルはapomorphine(dopamin agonist)及びMK801(NMDA-receptor antagonist)投与により、ipsiversive rotational behaviorを呈し、これは用量依存性であった。線条体虚血巣の神経終末についてsynaptophysinを指標にして経時的に検索すると2週目までは一過性にその発現が増加しており、4週後にはほとんど消失していた。これはtarget neuronを失ったnerve terminalの機能及び解剖学的変化を示しているものと考えている。また、線条体虚血巣に胎齢14〜15日のラット胎仔のstriatal promordiaを定位脳手術的に移植したところ、移植細胞は生着・成長を示し、手術後6ヵ月後の検索では、移植組織細胞の多くが中型有棘細胞のmarkerであるカルシウム・カルモデュリン依存性酵素(calcineurin及びCaM-kinase II)の免疫活性を有していた。さらに、移植細胞からは淡蒼球に対し、遠心性線維の投射が確認された。(投稿中)。今後更に一過性脳虚血に伴う大脳基底核障害の病態解析及び移植治療について検索を進める予定である。

研究成果

(12件)

すべてその他

すべて文献書誌 (12件)

[文献書誌] Satoshi Goto: "Striatonigral involvement following transient focal cerebral ischemia in the rats:an immunohistochemical study on a reversible ischemia model." Acta Neuropathologica. 85. 515-520 (1993)
[文献書誌] Kojiro Korematsu: "Changes of immunoreactivity for synaptophysin('protein p38')following tpansient cerebral ischemia in the rat striatum." Brain Research. 616. 320-324 (1993)
[文献書誌] Satoshi Goto: "Distinct neuronal subset reveals perikaryal immunostaining for synaptophysin('proteinp38')in the striatum of rats." Acta Neuropathologica. 86. 302-305 (1993)
[文献書誌] Satoshi Goto: "Neuronal induction of 72 kDa heat shock protein following methamphetamine-induced hyperthermia in the mouse hippocampus." Brain Research. 626. 351-356 (1993)
[文献書誌] Satoshi Goto: "NMDA receptor antagonist MK 801-induced circling behaviors in rats with unilateral striatal ischemic lesions or nigral 6-hydroxydopamine lesions." Acta Neuropathologica. 86. 480-483 (1993)
[文献書誌] Satoshi Goto: "Immunocytochemical localization of calcineurin in the adult and developing primary visual cortex of cats." Experimental Brain Research. 96. 377-386 (1993)
[文献書誌] Sinji Nagahiro: "Disruption of blood-cerebrospinal fluid barrier by transient cerebral ischemia." Brain Research. 633. 305-311 (1994)
[文献書誌] Satoshi Goto: "Subdivisional ischemic injury of the striatum causes apomorphine-induced rotational behavior in rats." Acta Neuropathologica. 87. 211-216 (1994)
[文献書誌] Satoshi Goto: "Laminar and columnar organization of immunoreactivity for calcineurin,a calcium and calmodulin-regulated protein phosphatase,in monkey striate cortex." Cerebral Cortex. in press.
[文献書誌] Kojiro Korematsu: "Microglial response to transient focal cerebral ischemia:an immunocyto-chemical study on the cerebral cortex using anti-phosphotyrosine antibody.21GC10:Journal of Cerebral Blood Flow and Metabolism" in press.
[文献書誌] Kazumichi Yamada: "Elevated immunoreactivity for glutamic acid decarboxylase(Mr 67 000)following transient middle cerebral artery occlusion in the rat cerebral cortex." Acta Neuropathologica. in press.
[文献書誌] Satoshi Goto: "Increased expression of growth-associated protein GAP-43/B-50 following cerebral hemitransection and striatal ischemic injury in the substanitia nigra of adult rats." Brain Research. in press.

1993 年度 実績報告書

脳血管障害性パーキンソニズムの病態解析とその外科的治療法の開発

研究代表者

後藤 恵 熊本大学, 医学部, 助手 (50240916)

研究成果

[文献書誌] Satoshi Goto: "Striatonigral involvement following transient focal cerebral ischemia in the rats:an immunohistochemical study on a reversible ischemia model." Acta Neuropathologica. 85. 515-520 (1993)

[文献書誌] Kojiro Korematsu: "Changes of immunoreactivity for synaptophysin('protein p38')following tpansient cerebral ischemia in the rat striatum." Brain Research. 616. 320-324 (1993)

[文献書誌] Satoshi Goto: "Distinct neuronal subset reveals perikaryal immunostaining for synaptophysin('proteinp38')in the striatum of rats." Acta Neuropathologica. 86. 302-305 (1993)

[文献書誌] Satoshi Goto: "Neuronal induction of 72 kDa heat shock protein following methamphetamine-induced hyperthermia in the mouse hippocampus." Brain Research. 626. 351-356 (1993)

[文献書誌] Satoshi Goto: "NMDA receptor antagonist MK 801-induced circling behaviors in rats with unilateral striatal ischemic lesions or nigral 6-hydroxydopamine lesions." Acta Neuropathologica. 86. 480-483 (1993)

[文献書誌] Satoshi Goto: "Immunocytochemical localization of calcineurin in the adult and developing primary visual cortex of cats." Experimental Brain Research. 96. 377-386 (1993)

[文献書誌] Sinji Nagahiro: "Disruption of blood-cerebrospinal fluid barrier by transient cerebral ischemia." Brain Research. 633. 305-311 (1994)

[文献書誌] Satoshi Goto: "Subdivisional ischemic injury of the striatum causes apomorphine-induced rotational behavior in rats." Acta Neuropathologica. 87. 211-216 (1994)

[文献書誌] Satoshi Goto: "Laminar and columnar organization of immunoreactivity for calcineurin,a calcium and calmodulin-regulated protein phosphatase,in monkey striate cortex." Cerebral Cortex. in press.

[文献書誌] Kojiro Korematsu: "Microglial response to transient focal cerebral ischemia:an immunocyto-chemical study on the cerebral cortex using anti-phosphotyrosine antibody.21GC10:Journal of Cerebral Blood Flow and Metabolism" in press.

[文献書誌] Kazumichi Yamada: "Elevated immunoreactivity for glutamic acid decarboxylase(Mr 67 000)following transient middle cerebral artery occlusion in the rat cerebral cortex." Acta Neuropathologica. in press.

[文献書誌] Satoshi Goto: "Increased expression of growth-associated protein GAP-43/B-50 following cerebral hemitransection and striatal ischemic injury in the substanitia nigra of adult rats." Brain Research. in press.

1993 年度実績報告書

後藤恵熊本大学, 医学部, 助手 (50240916)