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Article

Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models

  • Authors:
    • Bo Qiu
    • Xinguo Li
    • Xiyang Sun
    • Yong Wang
    • Zhitao Jing
    • Xu Zhang
    • Yunjie Wang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China, Liaoning Centers for Diseases Control and Prevention, Shenyang, Liaoning 110005, P.R. China
  • Pages: 916-922
    |
    Published online on: January 15, 2014
       https://doi.org/10.3892/mmr.2014.1899
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Abstract

‘Secondary insult’ following primary traumatic brain injury (TBI), including ischemia and edema, may aggravate brain impairments and affect the outcomes. The hippocampus is particularly sensitive to ischemia or edema due to its selective vulnerability, as neural cells of the hippocampus may be more prone to abnormal function or cell death in response to ischemia and edema. Aquaporin‑1 (AQP‑1) was reported to be associated with cerebral edema; however, the expression and role of AQP‑1 in hippocampal edema following TBI have seldom been investigated. In the current study, BALB/c mouse closed craniocerebral injury models were established and the changes of AQP‑1 expression in hippocampi of mouse models following TBI were investigated. Neurological function and edema formation of the models were evaluated and the apoptotic hippocampal cells were then stained in situ and detected, followed by determination of AQP‑1 expression in the hippocampus using immunohistochemistry and western blot analysis. As a result, the majority of mice in the TBI group were severely injured and hippocampal edema was confirmed. The apoptotic cells increased significantly in the hippocampi of mice in the TBI group compared with those in the sham group (P<0.01) and the apoptotic rate increased gradually in a time‑dependent manner. The expression levels of AQP‑1 in the hippocampi of mice were markedly higher in the TBI group than in the sham group (P<0.05) at various time points and AQP‑1 expression levels peaked one day following TBI. These results indicate that upregulation of AQP‑1 may participate in edema formation and delayed cell death of the hippocampus following TBI and may also be a novel therapeutic target to protect the hippocampus from secondary injury following TBI.
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1 

Greve MW and Zink BJ: Pathophysiology of traumatic brain injury. Mt Sinai J Med. 76:97–104. 2009. View Article : Google Scholar

2 

Borgens RB and Liu-Snyder P: Understanding secondary injury. Q Rev Biol. 87:89–127. 2012. View Article : Google Scholar

3 

Werner C and Engelhard K: Pathophysiology of traumatic brain injury. Br J Anaesth. 99:4–9. 2007. View Article : Google Scholar

4 

Padayachy LC, Rohlwink U, Zwane E, Fieggen G, Peter JC and Figaji AA: The frequency of cerebral ischemia/hypoxia in pediatric severe traumatic brain injury. Childs Nerv Syst. 28:1911–1918. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Walcott BP, Kahle KT and Simard JM: Novel treatment targets for cerebral edema. Neurotherapeutics. 9:65–72. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Adeva MM, Souto G, Donapetry C, Portals M, Rodriguez A and Lamas D: Brain edema in diseases of different etiology. Neurochem Int. 61:166–174. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Marmarou A: A review of progress in understanding the pathophysiology and treatment of brain edema. Neurosurg Focus. 22:E12007. View Article : Google Scholar : PubMed/NCBI

8 

Schmidt-Kastner R and Freund TF: Selective vulnerability of the hippocampus in brain ischemia. Neuroscience. 40:599–636. 1991. View Article : Google Scholar : PubMed/NCBI

9 

Royo NC, Conte V, Saatman KE, et al: Hippocampal vulnerability following traumatic brain injury: a potential role for neurotrophin-4/5 in pyramidal cell neuroprotection. Eur J Neurosci. 23:1089–1102. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Deng P and Xu ZC: Contribution of Ih to neuronal damage in the hippocampus after traumatic brain injury in rats. J Neurotrauma. 28:1173–1183. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Nawashiro H, Shima K and Chigasaki H: Selective vulnerability of hippocampal CA3 neurons to hypoxia after mild concussion in the rat. Neurol Res. 17:455–460. 1995.PubMed/NCBI

12 

Kawamata T, Katayama Y, Tsuji N and Nishimoto H: Metabolic derangements in interstitial brain edema with preserved blood flow: selective vulnerability of the hippocampal CA3 region in rat hydrocephalus. Acta Neurochir Suppl. 86:545–547. 2003.PubMed/NCBI

13 

Deng W, Aimone JB and Gage FH: New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 11:339–350. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Eichenbaum H: Hippocampus: cognitive processes and neural representations that underlie declarative memory. Neuron. 44:109–120. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Kim JE, Ryu HJ, Yeo SI, et al: Differential expressions of aquaporin subtypes in astroglia in the hippocampus of chronic epileptic rats. Neuroscience. 163:781–789. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Zelenina M: Regulation of brain aquaporins. Neurochem Int. 57:468–488. 2010. View Article : Google Scholar

17 

Tran ND, Kim S, Vincent HK, et al: Aquaporin-1-mediated cerebral edema following traumatic brain injury: effects of acidosis and corticosteroid administration. J Neurosurg. 112:1095–1104. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Badaut J, Lasbennes F, Magistretti PJ and Regli L: Aquaporins in brain: distribution, physiology, and pathophysiology. J Cereb Blood Flow Metab. 22:367–378. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Kim J and Jung Y: Increased aquaporin-1 and Na+-K+-2Cl− cotransporter 1 expression in choroid plexus leads to blood-cerebrospinal fluid barrier disruption and necrosis of hippocampal CA1 cells in acute rat models of hyponatremia. J Neurosci Res. 90:1437–1444. 2012.

20 

Ameli PA, Madan M, Chigurupati S, Yu A, Chan SL and Pattisapu JV: Effect of acetazolamide on aquaporin-1 and fluid flow in cultured choroid plexus. Acta Neurochir Suppl. 113:59–64. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Suzuki R, Okuda M, Asai J, et al: Astrocytes co-express aquaporin-1, -4, and vascular endothelial growth factor in brain edema tissue associated with brain contusion. Acta Neurochir Suppl. 96:398–401. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Chen Y, Constantini S, Trembovler V, Weinstock M and Shohami E: An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. J Neurotrauma. 13:557–568. 1996.PubMed/NCBI

23 

Albert-Weißenberger C, Várrallyay C, Raslan F, Kleinschnitz C and Sirén AL: An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice. Exp Transl Stroke Med. 4:12012.PubMed/NCBI

24 

Shapira Y, Shohami E, Sidi A, Soffer D, Freeman S and Cotev S: Experimental closed head injury in rats: mechanical, pathophysiologic, and neurologic properties. Crit Care Med. 16:258–265. 1988. View Article : Google Scholar : PubMed/NCBI

25 

Qiu B, Sun X, Zhang D, Wang Y, Tao J and Ou S: TRAIL and paclitaxel synergize to kill U87 cells and U87-derived stem-like cells in vitro. Int J Mol Sci. 13:9142–9156. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Stoica BA and Faden AI: Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics. 7:3–12. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Eisenberg HM, Gary HE Jr, Aldrich EF, et al: Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. J Neurosurg. 73:688–698. 1990. View Article : Google Scholar : PubMed/NCBI

28 

Donkin JJ and Vink R: Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol. 23:293–299. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Barzó P, Marmarou A, Fatouros P, Hayasaki K and Corwin F: Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging. J Neurosurg. 87:900–907. 1997.PubMed/NCBI

30 

Ito J, Marmarou A, Barzó P, Fatouros P and Corwin F: Characterization of edema by diffusion-weighted imaging in experimental traumatic brain injury. J Neurosurg. 84:97–103. 1996. View Article : Google Scholar : PubMed/NCBI

31 

Unterberg AW, Stover J, Kress B and Kiening KL: Edema and brain trauma. Neuroscience. 129:1021–1029. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Verkman AS, Yang B, Song Y, Manley GT and Ma T: Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice. Exp Physiol. 85(Spec No): 233S–241S. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Badaut J, Hirt L, Granziera C, Bogousslavsky J, Magistretti PJ and Regli L: Astrocyte-specific expression of aquaporin-9 in mouse brain is increased after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 21:477–482. 2001. View Article : Google Scholar : PubMed/NCBI

34 

Badaut J: Aquaglyceroporin 9 in brain pathologies. Neuroscience. 168:1047–1057. 2010. View Article : Google Scholar

35 

Wang Q, Ishikawa T, Michiue T, Zhu BL, Guan DW and Maeda H: Molecular pathology of pulmonary edema after injury in forensic autopsy cases. Int J Legal Med. 126:875–882. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Kobayashi H, Minami S, Itoh S, et al: Aquaporin subtypes in rat cerebral microvessels. Neurosci Lett. 297:163–166. 2001. View Article : Google Scholar : PubMed/NCBI

37 

Badaut J, Brunet JF, Grollimund L, et al: Aquaporin 1 and aquaporin 4 expression in human brain after subarachnoid hemorrhage and in peritumoral tissue. Acta Neurochir Suppl. 86:495–498. 2003.PubMed/NCBI

38 

Satoh J, Tabunoki H, Yamamura T, Arima K and Konno H: Human astrocytes express aquaporin-1 and aquaporin-4 in vitro and in vivo. Neuropathology. 27:245–256. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Jablonski EM, Webb AN, McConnell NA, Riley MC and Hughes FM Jr: Plasma membrane aquaporin activity can affect the rate of apoptosis but is inhibited after apoptotic volume decrease. Am J Physiol Cell Physiol. 286:C975–985. 2004.PubMed/NCBI

40 

Kim J and Jung Y: Different expressions of AQP1, AQP4, eNOS, and VEGF proteins in ischemic versus non-ischemic cerebropathy in rats: potential roles of AQP1 and eNOS in hydrocephalic and vasogenic edema formation. Anat Cell Biol. 44:295–303. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Blank ME and Ehmke H: Aquaporin-1 and HCO3(−)-Cl− transporter-mediated transport of CO2 across the human erythrocyte membrane. J Physiol. 550:419–429. 2003.PubMed/NCBI

42 

Staub F, Winkler A, Haberstok J, et al: Swelling, intracellular acidosis, and damage of glial cells. Acta Neurochir Suppl. 66:56–62. 1996.PubMed/NCBI

43 

Ringel F, Plesnila N, Chang RC, Peters J, Staub F and Baethmann A: Role of calcium ions in acidosis-induced glial swelling. Acta Neurochir Suppl. 70:144–147. 1997.PubMed/NCBI

44 

Plesnila N, Haberstok J, Peters J, Kolbl I, Baethmann A and Staub F: Effect of lactacidosis on cell volume and intracellular pH of astrocytes. J Neurotrauma. 16:831–841. 1999.PubMed/NCBI

45 

Ringel F, Chang RC, Staub F, Baethmann A and Plesnila N: Contribution of anion transporters to the acidosis-induced swelling and intracellular acidification of glial cells. J Neurochem. 75:125–132. 2000. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Qiu B, Li X, Sun X, Wang Y, Jing Z, Zhang X and Wang Y: Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models. Mol Med Rep 9: 916-922, 2014.
APA
Qiu, B., Li, X., Sun, X., Wang, Y., Jing, Z., Zhang, X., & Wang, Y. (2014). Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models. Molecular Medicine Reports, 9, 916-922. https://doi.org/10.3892/mmr.2014.1899
MLA
Qiu, B., Li, X., Sun, X., Wang, Y., Jing, Z., Zhang, X., Wang, Y."Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models". Molecular Medicine Reports 9.3 (2014): 916-922.
Chicago
Qiu, B., Li, X., Sun, X., Wang, Y., Jing, Z., Zhang, X., Wang, Y."Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models". Molecular Medicine Reports 9, no. 3 (2014): 916-922. https://doi.org/10.3892/mmr.2014.1899
Copy and paste a formatted citation
x
Spandidos Publications style
Qiu B, Li X, Sun X, Wang Y, Jing Z, Zhang X and Wang Y: Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models. Mol Med Rep 9: 916-922, 2014.
APA
Qiu, B., Li, X., Sun, X., Wang, Y., Jing, Z., Zhang, X., & Wang, Y. (2014). Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models. Molecular Medicine Reports, 9, 916-922. https://doi.org/10.3892/mmr.2014.1899
MLA
Qiu, B., Li, X., Sun, X., Wang, Y., Jing, Z., Zhang, X., Wang, Y."Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models". Molecular Medicine Reports 9.3 (2014): 916-922.
Chicago
Qiu, B., Li, X., Sun, X., Wang, Y., Jing, Z., Zhang, X., Wang, Y."Overexpression of aquaporin‑1 aggravates hippocampal damage in mouse traumatic brain injury models". Molecular Medicine Reports 9, no. 3 (2014): 916-922. https://doi.org/10.3892/mmr.2014.1899
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