Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema

Ao Xiong; Renping Xiong; Jing Yu; Yijia Liu; Ke Liu; Ge Jin; Jianzhong Xu; Jun Yan

doi:10.1093/burnst/tkaa050

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Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema

更新时间：2022-06-14

- Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema
- Burns & Trauma Vol. 9, Issue 1, (2021)
- 作者机构：
  
  1. Department of Orthopaedics
  2. State Key Laboratory of Trauma
  3. School of Life Science and Engineering
  4. Department of Biochemistry and Molecular Biology
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkaa050
  CLC：
- Published：2021，
  
  Published Online：15 March 2021，
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Ao Xiong, Renping Xiong, Jing Yu, Yijia Liu, Ke Liu, Ge Jin, Jianzhong Xu, Jun Yan, Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema, Burns & Trauma, Volume 9, 2021, tkaa050, https://doi.org/10.1093/burnst/tkaa050
DOI：

Ao Xiong, Renping Xiong, Jing Yu, Yijia Liu, Ke Liu, Ge Jin, Jianzhong Xu, Jun Yan, Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema, Burns & Trauma, Volume 9, 2021, tkaa050, https://doi.org/10.1093/burnst/tkaa050 DOI：

摘要

Abstract

BackgroundTraumatic brain edema (TBE) is caused by a specific water channel mediated by membrane aquaporins. Aquaporin-4 (AQP4) plays an especially important role in this process

but the relationship between AQP4 and TBE remains unclear. The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury (TBI)

as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.MethodsThe adult male Wistar rats we divided into a sham group and a TBI group

the latter of which was further divided into 1

24 and 72 hours (h) and 15 days (d) post injury subgroups. A proper TBI model was established

and brain edema was assessed in each group by water content. We measured the abundance of various proteins

including hypoxia inducible factor-1α (HIF-1α)

AQP4

microtubule-associated protein 2 (MAP2)

tau-5 protein

phosphorylated level of TAU

synaptophysin

cyclic adenosine monophosphate response element binding protein (CREB)

phosphorylated CREB and general control nonrepressed 2

in each group. Hippocampal neurons and spatial memory test were analyzed in different time points.ResultsCompared with that in the sham group

the level of AQP4 in hippocampal neurons began to significantly increase at 1 h post TBI and then decreased at 15 d post TBI. During this time frame

AQP4 level peaked at 12 and 72 h

and these peaks were closely correlated with high brain water content. HIF-1α displayed a similar trend. Conversely

levels of MAP2 began to decrease at 1 h post TBI and then increase at 15 d post TBI. In addition

the most severe brain edema in rats was found at 24 h post TBI

with neuronal loss and hippocampal dendritic spine injury. Compared to those in the sham group

rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time.ConclusionsAQP4 level was closely correlated with severity of brain edema

and abnormal levels thereof aggravated such severity after TBI.

关键词

Keywords

Aquaporin-4Brain edemaTraumatic brain injuryHypoxia inducible factor-1αMicrotubule-associated protein 2

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