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Protective Effects of Aquaporin-4 Deficiency on Longer-term Neurological Outcomes in a Mouse Model

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Abstract

Traumatic brain injury (TBI) has been a crucial health problem, with more than 50 million patients worldwide each year. Glymphatic system is a fluid exchange system that relies on the polarized water channel aquaporin-4 (AQP4) at the astrocytes, accounting for the clearance of abnormal proteins and metabolites from brain tissues. However, the dysfunction of glymphatic system and alteration of AQP4 polarization during the progression of TBI remain unclear. AQP4−/− and Wild Type (WT) mice were used to establish the TBI mouse model respectively. Brain edema and Evans blue extravasation were conducted 24 h post-injury to evaluate the acute TBI. Morris water maze (MWM) was used to establish the long-term cognitive functions of AQP4−/− and WT mice post TBI. Western-blot and qRT-PCR assays were performed to demonstrate protective effects of AQP4 deficiency to blood–brain barrier (BBB) integrity and amyloid-β clearance. The inflammation of cerebral tissues post TBI was estimated by ELISA assay. AQP4 deficiency alleviated the brain edema and neurological deficit in TBI mice. AQP4-knockout led to improved cognitive outcomes in mice post TBI. The BBB integrity and cerebral amyloid-β clearance were protected by AQP4 deficiency in TBI mice. AQP4 deficiency ameliorated the TBI-induced inflammation. AQP4 deficiency improved longer-term neurological outcomes in a mouse model of TBI.

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Funding

The study was supported by the Natural Science Foundation of Hebei Province, China (H2018206325 and H2020206543).

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Author notes

  1. Xiaosong Liu and Yingxin Xie have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, the Second Hospital of Hebei Medical University, No.215, Heping Road, Shijiazhuang, 050000, Hebei, China

    Xiaosong Liu, Xiangdong Wan, Jianliang Wu, Zhenzeng Fan & Lijun Yang

  2. Department of Doppler Ultrasound, the Second Hospital of Hebei Medical University, No.215, Heping Road, Shijiazhuang, 050000, Hebei, China

    Yingxin Xie

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  1. Xiaosong Liu
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Correspondence to Lijun Yang.

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Liu, X., Xie, Y., Wan, X. et al. Protective Effects of Aquaporin-4 Deficiency on Longer-term Neurological Outcomes in a Mouse Model. Neurochem Res 46, 1380–1389 (2021). https://doi.org/10.1007/s11064-021-03272-7

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  • DOI: https://doi.org/10.1007/s11064-021-03272-7

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