虚血性大脳基底核障害:動物モデルを用いた病態解折、移植治療に関する実験的研究

• Project/Area Number: 06671403
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Kumamoto University
• Principal Investigator: 後藤 恵 熊本大学, 医学部・附属病院, 講師 (50240916)
• Co-Investigator(Kenkyū-buntansha): 永廣 信治 熊本大学, 医学部・附属病院, 講師 (60145315) ; 生塩 之敬 熊本大学, 医学部, 教授 (20028583)
• Project Period (FY): 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥1,800,000 (Direct Cost: ¥1,800,000); Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: striatum / neuronal death / cerebral ischemia / substntia nigra / basal ganglia / transplantation / plasticity

Research Abstract

中大脳動脈閉塞ひよる一過性脳虚血を施したラットでは線条体に遅発性神経細胞障害が生じる。これに伴い黒質、淡蒼球固有の神経細胞に経シナプス性変性がみられ、それは線条体に虚血負荷が及んだ後、早期に起こることを確認した[Goto et al.,Brain Res,647:333-339,1994;Yamada.Goto et al.,Neuroscience 62:793-801,1994]。この興味深い現象は線条体からのGABA作動性抑制性投射線維の脱落による黒質、淡蒼球神経細胞の過興奮によるものと考えられ、GABA agonistであるmuscimolの持続脳室内投与によって、経シナプス性神経細胞死はほぼ完全に抑制された[Yamada,Goto et al(投稿中)]。なお、本動物モデルの虚血性障害を有する線条体に胎仔線条体原基細胞を移植すると、6ケ月後の検索で移植組織の生着、成長を確認し、それが線条体神経細胞の分化の指標となるcalcineurin,type II Ca^<2+>/calmodulin-dependent protein kinaseを発現していることを見い出し、また、移植組織から淡蒼球への遠心生投射線維が再構成されていることも確認した[Goto et al.,Neuroscience 62;,695-705,1994]。現在、上記の経シナプス性神経細胞死を抑制しつつ、胎仔神経細胞移植を行い、大脳基底核神経回路網の再構築を試みている。

Research Products

• [Publications] Goto S.: "Neostriatal mosaic and type II Ca^<2+>/calmodulin-dependent protein kinase:an immunohistchemical study on the adult rat striatum." Neurosci.Lett.173. 177-180 (1994)
• [Publications] Goto S.: "Increased exspression of growth-associated protein GAP-43/B-50 following cerebral hemitransection or striatal ischemic injury in the substantia nigra of adult rats." Brain Res.647. 333-339 (1994)
• [Publications] Yamada K.: "Elevated immunoreactivity for glutamic acid decarboxylase(Mr 67000)following transient middle cerebral artery occlusion in the rat cerebral cortex." Acta Neuropathol.88. 55-59 (1994)
• [Publications] Korematsu K.: "Microglial response to transient focal cerebral ischemia:an immunocytochemical study on the cerebral cortex using antiphosphotyrosine antibody." J.Cereb.Blood Flow Metab.14. 825-830 (1994)
• [Publications] Goto S.: "Cellular localization of type II Ca^<2+>/calmodulin-dependent protein kinase in the rat basal ganglia and intrastriatal grafts derived from fetal striatal primordia,in comparison with that of Ca^<2+>/calmodulin-regulated protein phosphatase,calcineurin." Neuroscience.62. 695-705 (1994)
• [Publications] Yamada K.: "Occurrence of heat shock response in the deafferented neurons of hte rat substantia rigra." Neuroscience.62. 793-801 (1994)
• [Publications] Goto S.: "Laminar and columnar organization of immunoreactivity for calcineurin,a calcium and calmodulin-regulated protein phosphatase,in monkey striate cortex." Cerebral Cortex.6. 636-645 (1994)
• [Publications] Yamada K.: "In vivo expresson of the growth asociated protein GAP-43/B-50 in rat macroglia following transient middle cerebral artery occlusion." Acta Neurophathol.88. 553-557 (1994)
• [Publications] Yamada K.: "Striatal cells containing the Ca^<2+>-binding protein calretinin in the ischemia-induced neuronal injury." Acta Neurophathol.(in press).