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Nimodipine Attenuates Early Brain Injury by Protecting the Glymphatic System After Subarachnoid Hemorrhage in Mice

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Abstract

The glymphatic system (GS) plays an important role in subarachnoid hemorrhage (SAH). Nimodipine treatment provides SAH patients with short-term neurological benefits. However, no trials have been conducted to quantify the relationship between nimodipine and GS. We hypothesized that nimodipine could attenuate early brain injury (EBI) after SAH by affecting the function of the GS. In this study, we assessed the effects of nimodipine, a dihydropyridine calcium channel antagonist, on mice 3 days after SAH. The functions of GS were assessed by immunofluorescence and western blot. The effects of nimodipine were assessed behaviorally. Concurrently, correlation analysis was performed for the functions of GS, immunofluorescence and behavioral function. Our results indicated that nimodipine improved GS function and attenuated neurological deficits and brain edema in mice with SAH. Activation of the cAMP/PKA pathway was involved in this process. GS function was closely associated with perivascular AQP4 polarization, cortical GFAP/AQP4 expression, brain edema and neurobehavioral function. In conclusion, this study shows for the first time that nimodipine plays a neuroprotective role in the period of EBI after SAH in mice through the GS.

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Acknowledgements

This work was supported by the Natural Science Foundation of Tianjin (No. 20JCZDJC00300), Tianjin Medical University Clinical Research Program (No. 2018kylc008).

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  1. Changkai Hou and Quanlei Liu have contributed equally to this work

Authors and Affiliations

  1. Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China

    Changkai Hou, Quanlei Liu, Hao Zhang, Bangyue Wang, Jian Li & Xinyu Yang

  2. Department of Neurosurgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China

    Weihan Wang

  3. Department of Neurosurgery, Tianjin Fifth Central Hospital, 41 Zhejiang Road, Binhai New Area, Tianjin, 300450, People’s Republic of China

    Xiaopeng Cui

  4. The Affiliated Suzhou Hospital of Nanjing Medical University, 242 Guangji Road, Suzhou, 215008, Jiangsu, People’s Republic of China

    Wen Ren

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  1. Changkai Hou
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Contributions

(I) Experimental design: XY; (II) Functional measurement of the glymphatic system: CH and QL; (III) Immunofluorescence and WB of AQP4 and GFAP: HZ and WW; (IV) SAH Mouse modeling: BQ; (V) Behavioral experiments in mice and measure the Blood Pressure: JL; (VI) Statistical analysis: XC and WR; (VII) Manuscript writing: All authors; (VIII) Final approval of manuscript: All authors.

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Correspondence to Xinyu Yang.

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Hou, C., Liu, Q., Zhang, H. et al. Nimodipine Attenuates Early Brain Injury by Protecting the Glymphatic System After Subarachnoid Hemorrhage in Mice. Neurochem Res 47, 701–712 (2022). https://doi.org/10.1007/s11064-021-03478-9

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