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Pentylentetrazole-induced loss of blood-brain barrier integrity involves excess nitric oxide generation by neuronal nitric oxide synthase
https://kagawa-u.repo.nii.ac.jp/records/197
https://kagawa-u.repo.nii.ac.jp/records/197a2a46ddf-d781-420f-88fb-9258af9bd572
| 名前 / ファイル | ライセンス | アクション |
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内容の要旨 (295.0 kB)
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審査の結果の要旨 (305.7 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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| 公開日 | 2014-03-24 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Pentylentetrazole-induced loss of blood-brain barrier integrity involves excess nitric oxide generation by neuronal nitric oxide synthase | |||||||||||||
| 言語 | en | |||||||||||||
| 言語 | ||||||||||||||
| 言語 | eng | |||||||||||||
| 資源タイプ | ||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||||
| 資源タイプ | doctoral thesis | |||||||||||||
| 著者 |
檀上, 園子
× 檀上, 園子
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Dysfunction of the blood–brain barrier (BBB) is one of the major pathophysiological consequences of epilepsy. The increase in the permeability caused by BBB failure is thought to contribute to the development of epileptic outcomes. We developed a method by which the BBB permeability can be demonstrated by gadolinium-enhanced T1 weighted imaging (GdET1WI). The present study examined the changes in the BBB permeability in mice with generalized convulsive seizures (GCS) induced by acute pentylentetrazole (PTZ) injection. At 15 min after PTZ-induced GCS, the BBB temporarily leaks BBB-impermeable contrast agent into the parenchyma of the diencephalon, hippocampus and cerebral cortex in mice, and the loss of BBB integrity was gradually recovered by 24 h. The temporary BBB failure is a critical link to the glutamatergic activities that occur following the injection of PTZ. PTZ activates the glutamatergic pathway via the NMDA receptor, then nitric oxide (NO) is generated by NMDA receptor-coupled neuronal NO synthase (nNOS). To examine the influence of nNOS-derived NO induced by PTZ on the increases of the BBB permeability, GdET1WI was performed using conventional nNOS gene-deficient mice with or without PTZ injection. The failure of the BBB induced by PTZ was completely protected by nNOS deficiency in the brain. These results suggest that nNOS-derived excess NO in the glutamatergic pathway plays a key role in the failure of the BBB during PTZ-induced GCS. The levels of NO synthetized by nNOS in the brain may represent an important target for the future development of drugs to protect the BBB. | |||||||||||||
| 言語 | en | |||||||||||||
| 学位名 | ||||||||||||||
| 言語 | ja | |||||||||||||
| 学位名 | 博士（医学） | |||||||||||||
| 学位授与機関 | ||||||||||||||
| 識別子Scheme | kakenhi | |||||||||||||
| 識別子 | 16201 | |||||||||||||
| 言語 | ja | |||||||||||||
| 機関名 | 香川大学 | |||||||||||||
| 言語 | en | |||||||||||||
| 機関名 | Kagawa University | |||||||||||||
| 学位授与年月日 | ||||||||||||||
| 学位授与年月日 | 2014-03-24 | |||||||||||||
| 学位授与番号 | ||||||||||||||
| 学位授与番号 | 甲第582号 | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報 | Copyright © 2013 Elsevier B.V. All rights reserved. | |||||||||||||
| PubMed番号 | ||||||||||||||
| 識別子タイプ | PMID | |||||||||||||
| 関連識別子 | 23831997 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | isVersionOf | |||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | https://doi.org/10.1016/j.brainres.2013.06.043 | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Blood–brain barrier | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Generalized convulsive seizures | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Gd-HP-DO3A | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | MRI | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Nitric oxide | |||||||||||||
| キーワード | ||||||||||||||
| 言語 | en | |||||||||||||
| 主題Scheme | Other | |||||||||||||
| 主題 | Pentylenetetrazole | |||||||||||||
| KEID | ||||||||||||||
| 27465 | ||||||||||||||
