Persistent brain exposure to high sodium induces stroke onset by upregulation of cerebral microbleeds and oxidative stress in hypertensive rats.

Sosho Kajiwara, Yu Hasegawa, Kana Fujimori, Satoshi Tomiyasu, Koki Kameno, Hiroki Uchikawa, Motohiro Morioka

Hypertension research : official journal of the Japanese Society of Hypertension 2024 Jan

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High salt intake induces hypertension and enhances stroke onset. However, whether an increase in brain sodium exposure itself is harmful and has poor prognosis remains unknown. Therefore, we employed hypertensive rats that underwent intracerebroventricular (ICV) infusion of sodium for 28 days and evaluated stroke onset and related cytotoxic brain injuries. Forty-seven spontaneously hypertensive stroke-prone (SHRSP) and 39 normotensive rats (Wistar Kyoto rats [WKY]) underwent persistent ICV infusion of the following four solutions: artificial cerebrospinal fluid, 0.9%, 2.7%, and 9% saline for 28 days. We evaluated stroke onset and all-cause mortality between SHRSP and WKY at each ICV sodium concentration as the primary endpoints. Our secondary objective was to explore histological brain injuries associated with SHRSP induced by high sodium ICV. The results indicated that ICV infusion of 2.7% and 9% sodium showed a significant increase in stroke onset, decrease in body weight, and increase rate of brain water content in SHRSP compared to WKY. Increased blood pressure was not observed for ICV infusion of high sodium, while serum sodium concentration was significantly increased in SHRSP compared to WKY. Histological evaluations revealed that higher sodium infusion significantly increased the number of activated microglia, superoxide, neuronal cell loss, and microbleeds compared to WKY and SHRSP with 0.9% sodium. We conclude that persistent exposure to high sodium in the brain is one of the risk factors for stroke onset upregulating cerebral microbleeds and oxidative stress in hypertensive rats. © 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.

Citation

Sosho Kajiwara, Yu Hasegawa, Kana Fujimori, Satoshi Tomiyasu, Koki Kameno, Hiroki Uchikawa, Motohiro Morioka. Persistent brain exposure to high sodium induces stroke onset by upregulation of cerebral microbleeds and oxidative stress in hypertensive rats. Hypertension research : official journal of the Japanese Society of Hypertension. 2024 Jan;47(1):78-87