{"created":"2023-07-27T06:58:38.447740+00:00","id":57422,"links":{},"metadata":{"_buckets":{"deposit":"ca24292a-c93f-4cf0-bf41-bc33c90aeef1"},"_deposit":{"created_by":18,"id":"57422","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"57422"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00057422","sets":["2812:2813:2830"]},"author_link":["99425","21831"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2005-04-18","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2002 – 2003","bibliographic_titles":[{"bibliographic_title":"平成15(2003)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要"},{"bibliographic_title":"2003 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"中枢神経の再生をめざして、これまでneurotrophins(NGF、BDNF、NT-3等)、neural cytokine(FGF, interleukin、TGF-beta、CNTF等)、接着因子(L1、cadherin、integrin)等の研究がなされ、最近では多彩な潜在能力を持つ神経幹細胞のParkinson病等の疾患の治療への応用の可能性が脚光をあびている。しかしながら、損傷されたmotoneuronの機能回復に関しては、いまだ治療へのbreakthroughが得られていないのが現状である.本研究では、まず定位脳手術操作により作成する脳幹内顔面神経軸索損傷モデルを確立した。我々のモデルはIto等の方法(J Neurophysiol 1996)を改良したもので、乏突起膠細胞に被覆された部位である中枢神経軸索の損傷であり、その損傷の確実性、再現性を確認したところ、約8割の顔面神経核ニューロンが脱落する中枢部位損傷モデルより、さらにニューロンの脱落が激しいもので、顔面神経核の残存神経細胞はday7で約3割、day28ではわずか2%まで低下していた。この激しい神経脱落は、Waller変性による末梢神経軸索の変牲に加え、末梢部位の軸索損傷ではほとんどみられない逆行性変性による神経細胞の脱落である。このモデルにおけるマトリックス・メタロプロテアーゼ(MMPs、特にMMPs2、9)に注目したところ、MMP-9はin situ zymographyでは脳幹内損傷部位周辺に特異的にgelatinase activityをみた。また、zymographyでは、損傷部とともに顔面神経核領域にMMP-9の活性上昇を確認した。ただしこれはまだ活性型と非活性型の区別はついていない。一方、MMP-2の活性上昇は見られなかった。次に、本モデルに脳幹内末梢神経移植を行ったところ、驚くべきことにday7で30%、day28で約10倍の数の神経細胞が生存している知見を得た。移植末梢神経組織内には、前述の各種成長因子が内在することが知られており、これらの作用が相乗効果をもって逆行性変性を抑制しえたものと考えられた。さらに、最近その造血因子としての作用に加え神経成長因子としての作用を併せ持つ可能性が注目されつつあるエリスロポイエチンを連日腹腔内投与したところ、day14で約7割の生存細胞の増加、day28では、約4倍の生存細胞の増加作用を確認した。現在、このエリスロポイエチンの運動神経細胞の逆行性変性抑制効果の作用機序をNOに注目し、検討中である。","subitem_description_type":"Abstract"},{"subitem_description":"The aim of this study is to establish a model to investigate the unknown mechanism of retrograde neuronal cell death in the facial nucleus after axotomy at various lesions.In addition, the neuroprotective effects of autografted peripheral nerve tissues, and alteration of MMPs expression are investigated.The models include brainstem injury model ; the genu of the facial nerve tract in the brainstem is stereotactically transected, control injury model ; the brainstem near the facial nucleus is injured without transection of the facial nerve tract, distal injury model ; the facial nerve is cut at the stylomastoid foramen, proximal injury model ; the facial nerve is avuked at the stylomastoid foramen resulting in more proximal transection than the distal injury model, and transplanted model ; PNS autograft is transplanted to the injury site of the brainstem injury model.On day 7, compared with the contralateral side, the survival ratio of motoneurons of the facial nuclei is 105.8±3.8% in the control injury group, 102.4±5.2% in the distal injury group; 94.6±7.4% in the proximal injury group, 30.9±8.3% in the brainstem injury group, 43.7±6.2% in the transplanted group. On day 28, the survival ratio is 96.4±5.0% in the control injury group, 90.2±3.0% in the distal injury group, 49.7±6.3% in the proximal injury group, 2.3±1.2% in the brainstem injury group, 20.4±5.1% in the transplanted group. In gelatin zymography and immunobistochemistry MIMiP-9 was expressed in injury site on day 1 with a peak on day 3.MMP-2 was expressed on day 1 and lasted for 7 days. In situ zymography showed gelatinase activity at the lesion site.These results suggest that the brainstem lesion model used in this study causes a massive neuronal cell death and this was partialiy rescued by the PNS autograft transplantation. MIMPs may play a role to regulate migration of inflammatory cells at the early stage of the injury.The transplantation of the PNS autograft has significant neuroprotective effects for retrograde degeneration.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:14571302, 研究期間(年度):2002 – 2003","subitem_description_type":"Other"},{"subitem_description":"出典：「中枢神経損傷後の細胞外基質分解酵素の発現変化と細胞遊走・軸索伸長抑制機構の解明」研究成果報告書　課題番号14571302\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14571302/145713022003kenkyu_seika_hokoku_gaiyo/)を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学系研究科","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063692","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/search/?kw=70218460"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=70218460","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-14571302/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-14571302/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14571302/145713022003kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14571302/145713022003kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-10-22"}],"displaytype":"detail","filename":"ME-PR-HASEGAWA-M-kaken 2005-2p.pdf","filesize":[{"value":"69.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-HASEGAWA-M-kaken 2005-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/57422/files/ME-PR-HASEGAWA-M-kaken 2005-2p.pdf"},"version_id":"4323c093-0eb6-4492-94d2-97e4b3bc8ad8"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"中枢神経損傷後の細胞外基質分解酵素の発現変化と細胞遊走・軸索伸長抑制機構の解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"中枢神経損傷後の細胞外基質分解酵素の発現変化と細胞遊走・軸索伸長抑制機構の解明"},{"subitem_title":"Retrograde neuronal cell death in the facial nucleus after axotomy in the brainstem -alteration of MMPs expression, cell migration and axonal regrowth-","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2830"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-10-22"},"publish_date":"2021-10-22","publish_status":"0","recid":"57422","relation_version_is_last":true,"title":["中枢神経損傷後の細胞外基質分解酵素の発現変化と細胞遊走・軸索伸長抑制機構の解明"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:36:32.534142+00:00"}