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脳血管障害と虚血 2
Cerebrovascular Disease and Ischemia 2

開催日 2014/9/13
時間 18:10 - 19:10
会場 Room I(311+312)
Chairperson(s) 冨本 秀和 / Hidekazu Tomimoto (三重大学大学院 医学系研究科 神経病態内科学 / Department of Neurology, Mie University, Japan)
阿部 康二 / Koji Abe (岡山大学大学院医歯薬学総合研究科神経病態内科学(神経内科) / Department of Neurology, Okayama University, Japan)

Contribution of the cortico-rubral pathway to the recovery of skilled forelimb movements through CIMT after capsular hemorrhage in rats

  • O3-I-6-3
  • 石田 章真 / Akimasa Ishida:1 伊佐 かおる / Kaoru Isa:2 小林 憲太 / Kenta Kobayashi:3 梅田 達也 / Tatsuya Umeda:2 伊佐 正 / Tadashi Isa:2 飛田 秀樹 / Hideki Hida:1 
  • 1:名古屋市立大学大学院 / Nagoya City Univ. Grad. Sch. Med. Sci., Japan 2:自然科学研究機構 生理学研究所 認知行動発達機構 / Dept. Dev. Physiol., Natl. Inst. Physiol. Sci., Okazaki, Japan 3:自然科学研究機構 生理学研究所 ウイルスベクター開発室 / Div. Viral Vector Dev, Natl, Inst. Physiol. Sci., Okazaki, Japan 

Constraint-induced movement therapy (CIMT) induces plastic changes of the residual brain after stroke. However, the circuit-level reorganization caused by CIMT and its causal relationship with functional recovery is still unclear. To elucidate these questions, we investigated the role of the reorganized motor circuits in CIMT-treated rat with stroke using double vector-infection technique for pathway-selective blockade. Wistar rats were divided into a sham-operated group, internal capsule hemorrhage (ICH) group, and ICH-CIMT group. ICH was induced by collagenase injection (15 Units/ml, 1.4 µl) into the internal capsule. CIMT group rats wore a one-sleeve cast to restrain their intact forelimb for a week. Behavioral assessments (skilled reaching and ladder stepping) showed better recovery in ICH-CIMT group than in ICH only group. Mapping of the ipsilesional motor cortex revealed that ICH-CIMT group demonstrated larger forelimb representative area compared to ICH group on days 10 and 26. Moreover, microinjection of muscimol (1 µM, 1 µl) into the newly-emerged forelimb areas resulted in impairment of the recovered forelimb movements. Next, we injected biotin dextran amine (BDA) into the same areas to trace axons projecting from these sites. As results, abundant BDA-positive fibers were found around ipsilateral red nucleus. Finally, we used a double-infection technique to block the cortico-rubral pathway selectively (Kinoshita et al., 2012; Sooksawate et al. 2013). A retrograde gene transfer vector with the gene encording enhanced tetanus neurotoxin under the control of a tetracycline responsive element was injected into the red nucleus and subsequent injection of adeno-associated viral vector with a highly efficient Tet-ON sequence at the motor cortex. After 6 weeks, impairment of skilled reaching task of ICH-CIMT group was found when the administration of doxycycline was initiated. These data suggested that the CIMT promoted reorganization of the ipsilesional motor cortex and enhanced the connection of cortico-rubral pathway as a substrate for functional recovery.

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