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
- Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema
- Burns & Trauma 2021年9卷第1期
- 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：
  
  Not applicable.
- DOI：10.1093/burnst/tkaa050
  中图分类号：
- 纸质出版日期：2021，
  
  网络出版日期：2021-3-15，
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Ao Xiong, Renping Xiong, Jing Yu, 等. Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema[J]. Burns & Trauma, 2021,9(1).

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
Ao Xiong, Renping Xiong, Jing Yu, 等. Aquaporin-4 is a potential drug target for traumatic brain injury via aggravating the severity of brain edema[J]. Burns & Trauma, 2021,9(1). DOI： 10.1093/burnst/tkaa050.

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

references

1. Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018;1:1–18.

2.Zelinkova V, Brazinova A, Taylor MS, Rusnak M, Plancikova D, Melichova J, et al. Location of traumatic brain injury-related deaths: epidemiological analysis of 11 European countries. Brain Inj. 2019;33:830–5.

3.Stubbs JL, Thornton AE, Sevick JM, Silverberg ND, Barr AM, Honer WG, et al. Traumatic brain injury in homeless and marginally housed individuals: a systematic review and meta-analysis. Lancet Public Health. 2020;5:e19–32.

4.Shenaq M, Kassem H, Peng C, Schafer S, Ding JY, Fredrickson V, et al. Neuronal damage and functional deficits are ameliorated by inhibition of aquaporin and HIF-1a after traumatic brain injury (TBI). J Neurol Sci. 2012;323:134–40.

5.Chen JQ, Xia QJ Lu H. Changes in AQP4 level and the pathology of injured cultured astrocytes after AQP4 mRNA silencing. Neuropsychiatry (London). 2017;7:426–32.

6.Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons. Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24:S1–106.

7.Higashida T, Kreipke CW, Rafols JA, Peng C, Schafer S, Schafer P, et al. The role of hypoxia-inducible factor-1alpha, aquaporin-4, and matrix metalloproteinase-9 in blood–brain barrier disruption and brain edema after traumatic brain injury. J Neurosurg. 2011;114:92–101.

8.Ho JD, Yeh R, Sandstrom A, Chorny I, Harries WE, Robbins RA, et al. Crystal structure of human aquaporin 4 at 1.8A and its mechanism of conductance. Proc Natl Acad Sci U S A. 2009;106:7437–42.

9.Verkman AS. Aquaporins at a glance. J Cell Sci. 2011;124:2107–12.

10.Scharfman HE, Binder DK. Aquaporin-4 water channels and synaptic plasticity in the hippocampus. Neurochem Int. 2013;63:702–11.

11.Szu JI, Binder DK. The role of astrocytic aquaporin-4 in synaptic plasticity and learning and memory. Front Integr Neurosci. 2016;10:8.

12.Yu LS, Fan YY, Ye G, Li J, Feng XP, Lin K, et al. Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage. Exp Ther Med. 2016;11:709–16.

13.Feeney DM, Boyeson MG, Linn RT, Murray HM, Dail WG. Responses to cortical injury: methodology and local effects of contusions in the rats. Brain Res. 1981;211:67–77.

14.Xu L, Yang Y, Gao L, Zhao J, Cai Y, Huang J. Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life. Biochim Biophys Acta. 2015;1852:1298–310.

15.Phan A, Gabor CS, Favaro KJ, Kaschack S, Armstrong JN, MacLusky NJ. Low doses of 17beta-estradiol rapidly improve learning and increase hippocampal dendritic spines. Neuropsychopharmacology. 2012;37:2299–309.

16.Phan A, Lancaster KE, Armstrong JN, MacLusky NJ, Choleris E. Rapid effects of estrogen receptor alpha and beta selective agonists on learning and dendritic spines in female mice. Endocrinology. 2011;152:1492–502.

17.Zhao ZA, Ning YL, Li P, Yang N, Peng Y, Xiong RP, et al. Widespread hyperphosphorylated tau in the working memory circuit early after cortical impact injury of brain. Behav Brain Res. 2017;323:146–53.

18.Han JH, Kushner SA, Yiu AP, Cole CJ, Matynia A, Brown RA, et al. Neuronal competition and selection during memory formation. Science. 2007;316:457–60.

19.Costa-Mattioli M, Gobert D, Harding H, Herdy B, Azzi M, Bruno M, et al. Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2. Nature. 2005;436:1166–73.

20.Szczygielski J, Glameanu C, Müller A, Klotz M, Sippl C, Hubertus V, et al. Changes in posttraumatic brain edema in craniectomy-selective brain hypothermia model are associated with modulation of aquaporin-4 level. Front Neurol. 2018;9:799.

21.Yao X, Uchida K, Papadopoulos MC, Zador Z, Manley GT, Verkman AS. Mildly reduced brain swelling and improved neurological outcome in aquaporin-4 knockout mice following controlled cortical impact brain injury. J Neurotrauma. 2015;32:1458–64.

22.Papadopoulos MC, Krishna S, Verkman AS. Aquaporin water channels and brain edema. Mt Sinai J Med. 2002;69:242–8.

23.Guo Q, Sayeed I, Baronne LM, Hoffman SW, Guennoun R, Stein DG. Progesterone administration modulates AQP4 expression and edema after traumatic brain injury in male rats. Exp Neurol. 2006;198:469–78.

24.Ding JY, Kreipke CW, Speirs SL, Schafer P, Schafer S, Rafols JA. Hypoxia-inducible factor-1 alpha signaling in aquaporin upregulation after traumatic brain injury. Neurosci Lett. 2009;453:68–72.

25.Griesdale DE, Honey CR. Aquaporins and brain edema. Surg Neurol. 2004;l61:418–21.

26.Marmarou A. A review of progress in understanding the pathophysiology and treatment of brain edema. Neurosurg Focus. 2007;22:E1.

27.Neri M, Frati A, Turillazzi E, Cantatore S, Cipolloni L, Di Paolo M, et al. Immunohistochemical evaluation of aquaporin-4 and its correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 expressions in fatal traumatic brain injury. Int J Mol Sci. 2018;19:3544.

28.Cash A, Theus MH. Mechanisms of blood–brain barrier dysfunction in traumatic brain injury. Int J Mol Sci. 2020;21:3344.

29.Peters J, Daum I, Gizewski E, Forsting M, Suchan B. Associations evoked during memory encoding recruit the context-network. Hippocampus. 2009;19:141–51.

30.Banerjee S, Neveu P, Kosik KS. A coordinated local translational control point at the synapse involving relief from silencing and MOV10 degradation. Neuron. 2009;64:871.

31.Brittain JM, Chen L, Wilson SM, Brustovetsky T, Gao X, Ashpole NM, et al. Neuroprotection against traumatic brain injury by a peptide derived from the collapse in response mediator protein 2 (CRMP2). J Biol Chem. 2011;286:37778–92.

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