Neurological Surgery 脳神経外科33巻8号

2005年08月発行

総説

くも膜下出血に続発する正常圧水頭症とTGF-β1で誘導したマウス水頭症

著者： 多田剛¹ 本郷一博¹

所属機関： ¹信州大学医学部脳神経外科学教室

ページ範囲：P.751 - P.757

Ⅰ．はじめに

　1965年にAdams，Hakimらが中高年の認知症患者の中にアルツハイマー病や脳血管性認知症のほかに，脳脊髄圧が正常範囲内（200mmH₂O未満）で，髄液流路に明らかな閉塞がないにもかかわらず水頭症となっている患者群がいることを報告した¹⁾．これらの患者にシャント術を行うと症状が劇的に改善することから，正常圧水頭症は可逆的な認知症を呈する疾患の1つとして注目された．以来，正常圧水頭症にシャント術を行うという治療法は定着したが，現在まで診断を確定する決定的な手段はなく，その病態については依然未解明な部分が残っている．

　この病態を解明するためには臨床研究とともに動物モデルでの病態解明が欠かせない．これまで報告されている交通性水頭症の動物モデルとしてはラットの先天性水頭症の系統やvacciniaウイルスを感染させる方法があるが^11,31,61)，最も一般的なのはカオリン（はくとう土）を実験動物の大槽内に注入する方法である．しかし，これは第四脳室周囲の脳槽に異物反応を起こして髄液の流れを止めるいわば閉塞性水頭症のモデルで，必ずしも正常圧水頭症の病態を解析するのに適しているとは言えない^23,37)．

　1994年に筆者らは，くも膜下出血時に血小板より髄液中に多量に放出されるtransforming growth factor-β1（TGF-β1）が正常圧水頭症の発生に果たす役割を調べる目的でヒト型リコンビナントTGF-β1をマウスの頭蓋骨下に注入し，交通性水頭症が誘導できることを発見した⁵⁵⁾．本稿ではこれまでこの水頭症マウスを使って解析してきたくも膜下出血に続発する正常圧水頭症の病態を紹介するとともに，これまで解析されてきた正常圧水頭症での認知症の病態についてまとめてみる．

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