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大学・研究所にある論文を検索できる 「マカクサル内包局所梗塞後の時期および領域特異的マクロファージ/ミクログリア応答」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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マカクサル内包局所梗塞後の時期および領域特異的マクロファージ/ミクログリア応答

加藤, 隼平 筑波大学 DOI:10.15068/0002005400

2022.11.17

概要

脳卒中後のマクロファージ/ミクログリアの炎症応答は,運動機能回復を阻害する因子となることが示唆されている.これらの研究には主にげっ歯類モデルが用いられてきた.本研究では脳構造や筋骨格系がヒトに近いサルモデルを用いて,運動神経線維束が集まる内包後脚部の局所梗塞後のマクロファージ/ミクログリア増加の経時的変化を定量的に解析した.梗塞周囲においてマクロファージ/ミクログリアマーカーであるIonized calcium binding adapter protein 1(Iba 1)は梗塞後0日から2〜3週間に徐々に増加し,少なくとも6ヶ月まで持続した.げっ歯類モデルでは脳卒中後数日から1週間で増加がピークに達し,1ヶ月で沈静化することが分かっている.また,本モデルを用いた先行研究では,内包後脚部の起始細胞が存在する一次運動野第V層において大型錐体細胞(巨大錐体細胞)の逆行性萎縮または変性が認められた.本研究では,この領域におけるIba1陽性細胞が梗塞後数週間の間に一過性の増加を示すことを発見した.次に梗塞周囲および一次運動野第V層においてマクロファージ/ミクログリアの表現型マーカーであるCD68(組織貪食型),CD86(炎症型),CD206(抗炎症型)およびそれぞれ炎症型と抗炎症型から放出されるサイトカインであるインターロイキン-1β(IL-1β),IL-10の発現を調べたところ,慢性期における梗塞周囲と一次運動野の両方でマクロファージ/ミクログリアが抗炎症の役割を担うことが示唆された.一方で炎症応答は急性期の梗塞周囲にのみ認められた.げっ歯類では脳卒中後急性期以降に炎症性マクロファージ/ミクログリアが優勢になることが報告されている.したがって,マクロファージ/ミクログリアの増加パターンおよびその役割は霊長類とげっ歯類間で異なる可能性がある.

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