An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture

• Material Type: 博士論文
• Title: An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture
• Author/Editor: Shikata, Eiji; Miyamoto, Takeshi; Yamaguchi, Tadashi; Yamaguchi, Izumi; Kagusa, Hiroshi; Gotoh, Daiki; Shimada, Kenji; Tada, Yoshiteru; Yagi, Kenji; Kitazato, Keiko T.; Kanematsu, Yasuhisa; Takagi, Yasushi
• Author Heading: Shikata, Eiji; Miyamoto, Takeshi; Yamaguchi, Tadashi; Yamaguchi, Izumi; Kagusa, Hiroshi; Gotoh, Daiki; Shimada, Kenji; Tada, Yoshiteru; Yagi, Kenji; Kitazato, Keiko T.; Kanematsu, Yasuhisa; Takagi, Yasushi
• Publication, Distribution, etc.: Springer nature
• Publication Date: 2022-06-20
• Publication Date (W3CDTF): 2022-06-20
• Alternative Title: 破裂脳動脈瘤モデルにおけるRAGE/MR/HMGB1とATP1α3の不均衡は脳組織の炎症と関連する
• Periodical title: Journal of Neuroinflammation
• No. or year of volume/issue: 19
• Volume: 19
• Pages: 161-
• ISSN (Periodical Title): ISSN : 1742-2094
• Degree grantor/type: 徳島大学
• Date Granted: 2022-10-27
• Dissertation Number: 甲第3666号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: RAGE; mineral corticoid receptor; HMGB1; ATP1α3; intracranial aneurysm; brain; Brain damage; Cerebral aneurysm; SAH; MR
• Target Audience: 一般
• Note (General): Background and purpose: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3). Methods: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet. Results: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05). Conclusions: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.
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• Related Material (DOI): 10.1186/s12974-022-02526-7
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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