Skip to main content

Advertisement

SpringerLink
Log in

Aquaporin 4 regulation during acute and long-term experimental Herpes simplex virus encephalitis

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Structural damage of the central nervous system (CNS) often leads to severely disabling residual symptoms despite effective antiviral therapy during Herpes simplex virus encephalitis (HSVE). Edematous space-occupying lesions are pathological and neuroradiological well-known phenomena for this disease. The molecular mechanisms of brain edema development in HSVE are poorly understood, the regulation of water brain-blood barrier (BBB) permeability might be disturbed. Aquaporin 4 (AQP4) is the predominant aquaporin expressed in the brain. Aquaporin 1 (AQP1) plays a role in cerebrospinal fluid modulation. Previous studies suggest that alterations of AQP expression play an important role in the development of brain edema. The mRNA expression of AQP4, AQP1, of their physiologically associated proteins Alpha-syntrophin and KIR 4.1 and of the structural glial protein glial fibrillary acid protein (GFAP) was analyzed in a well-established mice model simulating the human disease. Our data demonstrate a significant down-regulation of AQP4 in the acute phase of disease and an up-regulation of AQP4 and AQP1 in the long term. These results reveal the complex transcription pattern of AQP4, AQP1, KIR 4.1, alpha-syntrophin, and GFAP during HSVE and suggest a role for AQP4 regulation in the pathophysiology of acute and long-term HSVE. AQP4 modulation could be a potential target for brain edema treatment during HSVE.

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

  • Alexander JJ, Bao L, Jacob A, Kraus DM, Holers VM, Quigg RJ (2003). Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation and aquaporin 4 expression in lupus cerebritis. Biochim Biophys Acta 1639: 169–176.

    CAS  PubMed  Google Scholar 

  • Amiry-Moghaddam M, Frydenlund DS, Ottersen OP (2004). Anchoring of aquaporin-4 in brain: molecular mechanisms and implications for the physiology and pathophysiology of water transport. Neuroscience 129: 999–1010.

    CAS  PubMed  Google Scholar 

  • Amiry-Moghaddam M, Otsuka T, Hurn PD, Traystman RJ, Haug FM, Froehner SC, Adams ME, Neely JD, Agre P, Ottersen OP, Bhardwaj A (2003). An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci U S A 100: 2106–2111.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Giovannoni G (2006). Neuromyelitis optica and anti-aquaporin-4 antibodies: widening the clinical phenotype. J Neurol Neurosurg Psychiatry 77: 1001–1002.

    Article  CAS  PubMed  Google Scholar 

  • Hudson SJ, Dix RD, Streilein JW (1991). Induction of encephalitis in SJL mice by intranasal infection with herpes simplex virus type 1: a possible model of herpes simplex encephalitis in humans. J Infect Dis 163: 720–727.

    CAS  PubMed  Google Scholar 

  • Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P (1994). Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci U S A 91: 13052–13056.

    Article  CAS  PubMed  Google Scholar 

  • Kiening KL, van Landeghem FK, Schreiber S, Thomale UW, von Deimling A, Unterberg AW, Stover JF (2002). Decreased hemispheric aquaporin-4 is linked to evolving brain edema following controlled cortical impact injury in rats. Neurosci Lett 324: 105–108.

    Article  CAS  PubMed  Google Scholar 

  • Lamadé UM, Lamade W, Hess T, Gosztonyi G, Kehm R, Sartor K, Hacke W (1996). A mouse model of herpes simplex virus encephalitis: diagnostic brain imaging by magnetic resonance imaging. In Vivo 10: 563–568.

    PubMed  Google Scholar 

  • Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005). IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202: 473–477.

    Article  CAS  PubMed  Google Scholar 

  • Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LM, Adams ME, Froehner SC, Yates JR, 3rd, Vandenberg CA (2004). Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins. J Biol Chem 279: 22331–22346.

    Article  CAS  PubMed  Google Scholar 

  • Lu H, Sun SQ (2003). A correlative study between AQP4 expression and the manifestation of DWI after the acute ischemic brain edema in rats. Chin Med J (Engl) 116: 1063–1069.

    CAS  Google Scholar 

  • Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000). Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6: 159–163.

    Article  CAS  PubMed  Google Scholar 

  • Markert JM, Fuller CM, Gillespie GY, Bubien JK, McLean LA, Hong RL, Lee K, Gullans SR, Mapstone TB, Benos DJ (2001). Differential gene expression profiling in human brain tumors. Physiol Genomics 5: 21–33.

    CAS  PubMed  Google Scholar 

  • Martinez-Torres FJ, Wagner S, Haas J, Kehm R, Sellner J, Hacke W, Meyding-Lamade U (2004). Increased presence of matrix metalloproteinases 2 and 9 in short- and long-term experimental herpes simplex virus encephalitis. Neurosci Lett 368: 274–278.

    Article  CAS  PubMed  Google Scholar 

  • McGrath N, Anderson NE, Croxson MC, Powell KF (1997). Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry 63: 321–326.

    Article  CAS  PubMed  Google Scholar 

  • Meyding-Lamadé U, Lamadé W, Kehm R, Oberlinner C, Fath A, Wildemann B, Haas J, Hacke W (1999a). Herpes simplex virus encephalitis: chronic progressive cerebral MRI changes despite good clinical recovery and low viral load—an experimental mouse study. Eur J Neurol 6: 531–538.

    Article  PubMed  Google Scholar 

  • Meyding-Lamadé UK, Lamadé WR, Wildemann BT, Sartor K, Hacke W (1999b). Herpes simplex virus encephalitis: chronic progressive cerebral magnetic resonance imaging abnormalities in patients despite good clinical recovery. Clin Infect Dis 28: 148–149.

    Article  PubMed  Google Scholar 

  • Meyding-Lamadé UK, Oberlinner C, Rau PR, Seyfer S, Heiland S, Sellner J, Wildemann BT, Lamadé WR (2003). Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities. J NeuroVirol 9: 118–125.

    PubMed  Google Scholar 

  • Nicchia GP, Frigeri A, Liuzzi GM, Svelto M (2003). Inhibition of aquaporin-4 expression in astrocytes by RNAi determines alteration in cell morphology, growth, and water transport and induces changes in ischemia-related genes. FASEB J 17: 1508–1510.

    CAS  PubMed  Google Scholar 

  • Oshio K, Watanabe H, Song Y, Verkman AS, Manley GT (2005). Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel aquaporin-1. FASEB J 19: 76–78.

    CAS  PubMed  Google Scholar 

  • Papadopoulos MC, Krishna S, Verkman AS (2002). Aquaporin water channels and brain edema. Mt Sinai J Med 69: 242–248.

    PubMed  Google Scholar 

  • Papadopoulos MC, Verkman AS (2005). Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis. J Biol Chem 280: 13906–13912.

    Article  CAS  PubMed  Google Scholar 

  • Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA (2006). Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 63: 964–968.

    Article  PubMed  Google Scholar 

  • Saadoun S, Papadopoulos MC, Krishna S (2003). Water transport becomes uncoupled from K+ siphoning in brain contusion, bacterial meningitis, and brain tumours: immunohistochemical case review. J Clin Pathol 56: 972–975.

    Article  CAS  PubMed  Google Scholar 

  • Schmutzhard E (2001). Viral infections of the CNS with special emphasis on herpes simplex infections. J Neurol 248: 469–477.

    Article  CAS  PubMed  Google Scholar 

  • Simmonds P, Balfe P, Peutherer JF, Ludlam CA, Bishop JO, Brown AJ (1990). Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol 64: 864–872.

    CAS  PubMed  Google Scholar 

  • St Hillaire C, Vargas D, Pardo CA, Gincel D, Mann J, Rothstein JD, McArthur JC, Conant K (2005). Aquaporin 4 is increased in association with human immunodeficiency virus dementia: implications for disease pathogenesis. J NeuroVirol 11: 535–543.

    Article  Google Scholar 

  • Steiner I, Kennedy PG (1995). Herpes simplex virus latent infection in the nervous system. J NeuroVirol 1: 19–29.

    Article  CAS  PubMed  Google Scholar 

  • Vajda Z, Pedersen M, Fuchtbauer EM, Wertz K, Stodkilde-Jorgensen H, Sulyok E, Doczi T, Neely JD, Agre P, Frokiaer J, Nielsen S (2002). Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice. Proc Natl Acad Sci U S A 99: 13131–13136.

    Article  CAS  PubMed  Google Scholar 

  • Warth A, Kroger S, Wolburg H (2004). Redistribution of aquaporin-4 in human glioblastoma correlates with loss of agrin immunoreactivity from brain capillary basal laminae. Acta Neuropathol (Berl) 107: 311–318.

    Article  CAS  Google Scholar 

  • Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG (2006). Revised diagnostic criteria for neuromyelitis optica. Neurology 66: 1485–1489.

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Zhang AQ, Yew DT (2005). Age related changes of various markers of astrocytes in senescence-accelerated mice hippocampus. Neurochem Int 46: 565–574.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    F. J. Martinez Torres, D. Völcker, N. Dörner, Th. Lenhard, S. Nielsen, J. Haas & U. Meyding-Lamadé

  2. Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany

    K. Kiening

Authors
  1. F. J. Martinez Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Völcker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Dörner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Th. Lenhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Haas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Kiening
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. U. Meyding-Lamadé
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. J. Martinez Torres.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martinez Torres, F.J., Völcker, D., Dörner, N. et al. Aquaporin 4 regulation during acute and long-term experimental Herpes simplex virus encephalitis. Journal of NeuroVirology 13, 38–46 (2007). https://doi.org/10.1080/13550280601145340

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280601145340

Keywords

Search

Navigation