Skip to main content
SpringerLink
Log in

Aquaporin-4 deficiency attenuates acute lesions but aggravates delayed lesions and microgliosis after cryoinjury to mouse brain

  • Original Article
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Objective

To determine whether aquaporin-4 (AQP4) regulates acute lesions, delayed lesions, and the associated microglial activation after cryoinjury to the brain.

Methods

Brain cryoinjury was applied to AQP4 knockout (KO) and wild-type mice. At 24 h and on days 7 and 14 after cryoinjury, lesion volume, neuronal loss, and densities of microglia and astrocytes were determined, and their changes were compared between AQP4 KO and wild-type mice.

Results

Lesion volume and neuronal loss in AQP4 KO mice were milder at 24 h following cryoinjury, but worsened on days 7 and 14, compared to those in wild-type mice. Besides, microglial density increased more, and astrocyte proliferation and glial scar formation were attenuated on days 7 and 14 in AQP4 KO mice.

Conclusion

AQP4 deficiency ameliorates acute lesions, but worsens delayed lesions, perhaps due to the microgliosis in the late phase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Saadoun S, Papadopoulos MC. Aquaporin-4 in brain and spinal cord oedema. Neuroscience 2010, 168: 1036–1046.

    Article  PubMed  CAS  Google Scholar 

  2. Yukutake Y, Yasui M. Regulation of water permeability through aquaporin-4. Neuroscience 2010, 168: 885–891.

    Article  PubMed  CAS  Google Scholar 

  3. Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol 2007, 22: 778–784.

    Article  PubMed  Google Scholar 

  4. Saadoun S, Papadopoulos MC, Watanabe H, Yan D, Manley GT, Verkman AS. Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J Cell Sci 2005, 118: 5691–5698.

    Article  PubMed  CAS  Google Scholar 

  5. Auguste KI, Jin S, Uchida K, Yan D, Manley GT, Papadopoulos MC, et al. Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury. FASEB J 2007, 21: 108–116.

    Article  PubMed  CAS  Google Scholar 

  6. Thrane AS, Rappold PM, Fujita T, Torres A, Bekar LK, Takano T, et al. Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci U S A 2011, 108: 846–851.

    Article  PubMed  CAS  Google Scholar 

  7. Ding JH, Sha LL, Chang J, Zhou XQ, Fan Y, Hu G. Alterations of striatal neurotransmitter release in aquaporin-4 deficient mice: An in vivo microdialysis study. Neurosci Lett 2007, 422: 175–180.

    Article  PubMed  CAS  Google Scholar 

  8. Taya K, Marmarou CR, Okuno K, Prieto R, Marmarou A. Effect of secondary insults upon aquaporin-4 water channels following experimental cortical contusion in rats. J Neurotrauma 2010, 27: 229–239.

    Article  PubMed  Google Scholar 

  9. Oliva AA Jr., Kang Y, Truettner JS, Sanchez-Molano J, Furones C, Yool AJ, et al. Fluid-percussion brain injury induces changes in aquaporin channel expression. Neuroscience 2011, 180: 272–279.

    Article  PubMed  CAS  Google Scholar 

  10. Rao KV, Reddy PV, Curtis KM, Norenberg MD. Aquaporin-4 expression in cultured astrocytes after fluid percussion injury. J Neurotrauma 2011, 28: 371–381.

    Article  PubMed  Google Scholar 

  11. Papadopoulos MC, Manley GT, Krishna S, Verkman AS. Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 2004, 18: 1291–1293.

    PubMed  CAS  Google Scholar 

  12. Hortobagyi T, Hortobagyi S, Gorlach C, Harkany T, Benyo Z, Gorogh T, et al. A novel brain trauma model in the mouse: effects of dexamethasone treatment. Pflugers Arch 2000, 441: 409–415.

    Article  PubMed  CAS  Google Scholar 

  13. Wang J, Takeuchi K, Ookawara S. Changes of perivascular macrophages in the process of brain edema induced by cold injury. Acta Neurochir Suppl 2003, 86: 281–285.

    Article  PubMed  CAS  Google Scholar 

  14. Moon C, Lee J, Ahn M, Shin T. Involvement of Disabled-2 protein in the central nervous system inflammation following experimental cryoinjury of rat brains. Neurosci Lett 2005, 378: 88–91.

    Article  PubMed  CAS  Google Scholar 

  15. Shin T, Ahn M, Kim H, Moon C, Kang TY, Lee JM, et al. Temporal expression of osteopontin and CD44 in rat brains with experimental cryolesions. Brain Res 2005, 1041: 95–101.

    Article  PubMed  CAS  Google Scholar 

  16. Quintana A, Giralt M, Rojas S, Penkowa M, Campbell IL, Hidalgo J, et al. Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury. J Neurosci Res 2005, 82: 701–716.

    Article  PubMed  CAS  Google Scholar 

  17. Koedel U, Merbt UM, Schmidt C, Angele B, Popp B, Wagner H, et al. Acute brain injury triggers MyD88-dependent, TLR2/4-independent inflammatory responses. Am J Pathol 2007, 171: 200–213.

    Article  PubMed  CAS  Google Scholar 

  18. Moon C, Ahn M, Kim S, Jin JK, Sim KB, Kim HM, et al. Temporal patterns of the embryonic intermediate filaments nestin and vimentin expression in the cerebral cortex of adult rats after cryoinjury. Brain Res 2004, 1028: 238–242.

    Article  PubMed  CAS  Google Scholar 

  19. Hirano S, Yonezawa T, Hasegawa H, Hattori S, Greenhill NS, Davis PF, et al. Astrocytes express type VIII collagen during the repair process of brain cold injury. Biochem Biophys Res Commun 2004, 317: 437–443.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang L, Zhang WP, Chen KD, Qian XD, Fang SH, Wei EQ. Caffeic acid attenuates neuronal damage, astrogliosis and glial scar formation in mouse brain with cryoinjury. Life Sci 2007, 80: 530–537.

    Article  PubMed  CAS  Google Scholar 

  21. Fan Y, Zhang J, Sun XL, Gao L, Zeng XN, Ding JH, et al. Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice. J Neurosci Res 2005, 82: 458–464.

    Article  PubMed  CAS  Google Scholar 

  22. Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 2000, 6: 159–163.

    Article  PubMed  CAS  Google Scholar 

  23. Trabold R, Schueler OG, Eriskat J, Plesnila N, Baethmann AJ, Back T. Arterial hypotension triggers perifocal depolarizations and aggravates secondary damage in focal brain injury. Brain Res 2006, 1071: 237–244.

    Article  PubMed  CAS  Google Scholar 

  24. Weinzierl MR, Laurer HL, Fuchs M, Wolf-Ingo S, Mautes AE. Changes in regional energy metabolism after cortical cold lesion in the rat brain. J Mol Neurosci 2002, 18: 247–250.

    Article  PubMed  CAS  Google Scholar 

  25. Kuppers E, Gleiser C, Brito V, Wachter B, Pauly T, Hirt B, et al. AQP4 expression in striatal primary cultures is regulated by dopamine — implications for proliferation of astrocytes. Eur J Neurosci 2008, 28: 2173–2182.

    Article  PubMed  Google Scholar 

  26. Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 2009, 32: 638–647.

    Article  PubMed  CAS  Google Scholar 

  27. Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 1999, 23: 297–308.

    Article  PubMed  CAS  Google Scholar 

  28. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2004, 24: 2143–2155.

    Article  PubMed  CAS  Google Scholar 

  29. Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 2006, 12: 829–834.

    Article  PubMed  CAS  Google Scholar 

  30. Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 2008, 28: 7231–7243.

    Article  PubMed  CAS  Google Scholar 

  31. Liedtke W, Edelmann W, Chiu FC, Kucherlapati R, Raine CS. Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion. Am J Pathol 1998, 152: 251–259.

    PubMed  CAS  Google Scholar 

  32. Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LB, Tiwari-Woodruff S, et al. Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 2009, 29: 11511–11522.

    Article  PubMed  CAS  Google Scholar 

  33. Aoki-Yoshino K, Uchihara T, Duyckaerts C, Nakamura A, Hauw JJ, Wakayama Y. Enhanced expression of aquaporin 4 in human brain with inflammatory diseases. Acta Neuropathol 2005, 110: 281–288.

    Article  PubMed  CAS  Google Scholar 

  34. Miyamoto K, Nagaosa N, Motoyama M, Kataoka K, Kusunoki S. Upregulation of water channel aquaporin-4 in experimental autoimmune encephalomyelitis. J Neurol Sci 2009, 276: 103–107.

    Article  PubMed  CAS  Google Scholar 

  35. Huang XN, Wang WZ, Fu J, Wang HB. The relationship between aquaporin-4 expression and blood-brain and spinal cord barrier permeability following experimental autoimmune encephalomyelitis in the rat. Anat Rec (Hoboken) 2011, 294: 46–54.

    Article  CAS  Google Scholar 

  36. Graber DJ, Levy M, Kerr D, Wade WF. Neuromyelitis optica pathogenesis and aquaporin 4. J Neuroinflammation 2008, 5: 22.

    Article  PubMed  Google Scholar 

  37. Hinson SR, McKeon A, Lennon VA. Neurological autoimmunity targeting aquaporin-4. Neuroscience 2010, 168: 1009–1018.

    Article  PubMed  CAS  Google Scholar 

  38. St Hillaire C, Vargas D, Pardo CA, Gincel D, Mann J, Rothstein JD, et al. Aquaporin 4 is increased in association with human immunodeficiency virus dementia: implications for disease pathogenesis. J Neurovirol 2005, 11: 535–543.

    Article  PubMed  CAS  Google Scholar 

  39. Martinez Torres FJ, Volcker D, Dorner N, Lenhard T, Nielsen S, Haas J, et al. Aquaporin 4 regulation during acute and long-term experimental Herpes simplex virus encephalitis. J Neurovirol 2007, 13: 38–46.

    Article  PubMed  CAS  Google Scholar 

  40. Wu H, Zhang Z, Li Y, Zhao R, Li H, Song Y, et al. Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema. Neurochem Int 2010, 57: 248–253.

    Article  PubMed  CAS  Google Scholar 

  41. Sharma R, Fischer MT, Bauer J, Felts PA, Smith KJ, Misu T, et al. Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination. Acta Neuropathol 2010, 120: 223–236.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Institute of Neurobiology, School of Medicine, Zhejiang University, Hangzhou, 310058, China

    Wen-Zhen Shi, Chun-Zhen Zhao, Bing Zhao, Xiao-Liang Zheng, San-Hua Fang, Yun-Bi Lu, Wei-Ping Zhang, Zhong Chen & Er-Qing Wei

Authors
  1. Wen-Zhen Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-Zhen Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Liang Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. San-Hua Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yun-Bi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei-Ping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Er-Qing Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Er-Qing Wei.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, WZ., Zhao, CZ., Zhao, B. et al. Aquaporin-4 deficiency attenuates acute lesions but aggravates delayed lesions and microgliosis after cryoinjury to mouse brain. Neurosci. Bull. 28, 61–68 (2012). https://doi.org/10.1007/s12264-012-1063-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-012-1063-7

Keywords

Search

Navigation