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

Hypertension Research volume 47, pages 78–87 (2024)Cite this article

Abstract

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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by research grants from The Salt Science Research Foundation (2034), JSPS KAKENHI (21K09193), and IUHW Research Grants.

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Authors and Affiliations

  1. Department of Neurosurgery, Kurume University School of Medicine, Fukuoka, Japan

    Sosho Kajiwara, Yu Hasegawa, Kana Fujimori & Motohiro Morioka

  2. Department of Pharmaceutical Sciences, School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, Japan

    Yu Hasegawa

  3. Department of Medical Technology and Sciences, School of Health Sciences at Fukuoka, International University of Health and Welfare, Fukuoka, Japan

    Satoshi Tomiyasu

  4. Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan

    Koki Kameno & Hiroki Uchikawa

Authors
  1. Sosho Kajiwara
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  4. Satoshi Tomiyasu
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  5. Koki Kameno
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  6. Hiroki Uchikawa
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  7. Motohiro Morioka
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Contributions

SK and YH contributed to study conception and design. SK, KF, ST, KK, and HU performed the experiments. YH performed the statistical analysis. MM helped with the interpretations. SK wrote the first draft of the manuscript. YH revised the manuscript. All authors reviewed and approved the manuscript.

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Correspondence to Yu Hasegawa.

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Kajiwara, S., Hasegawa, Y., Fujimori, K. et al. Persistent brain exposure to high sodium induces stroke onset by upregulation of cerebral microbleeds and oxidative stress in hypertensive rats. Hypertens Res 47, 78–87 (2024). https://doi.org/10.1038/s41440-023-01447-z

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