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

Qiu,Bo; Li,Xinguo; Sun,Xiyang; Wang,Yong; Jing,Zhitao; Zhang,Xu; Wang,Yunjie

doi:10.3892/mmr.2014.1899

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

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
Published online on: January 15, 2014 https://doi.org/10.3892/mmr.2014.1899
Pages: 916-922

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

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