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

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...

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Published in:Journal of neuroinflammation 2022-06, Vol.19 (1), p.1-161, Article 161
Main Authors: 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
Format: Article
Language:English
Subjects:
Advanced glycosylation end products
Aneurysm
Aneurysms
Antibodies
Arteries
Blood pressure
Brain damage
Brain injury
Cerebral aneurysm
Diet
Down-regulation
Gene expression
Glycosylation
HMGB1
HMGB1 protein
Inflammation
Laboratory animals
Ligands
Medical prognosis
mRNA
Na+/K+-exchanging ATPase
Ovariectomy
Parenchyma
Proteins
RAGE
S100b protein
SAH
Subarachnoid hemorrhage
Surgery
Veins & arteries
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Summary: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 
ISSN:1742-2094
1742-2094
DOI:10.1186/s12974-022-02526-7