Skip to main content
SpringerLink
Log in

Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059, decreases trauma-induced brain edema

  • Conference paper
Acta Neurochirurgica Supplements

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 102))

Background Currently, there are no pharmacological treatments available for traumatically induced brain edema and the subsequent rise of ICP. Evidence indicates that Aqua-porin-4 (AQP4) plays a significant role in the pathophys-iology of brain edema. Previously we have reported that SR49059 reduced brain edema secondary to ischemia. We, therefore, examined whether the selective V1a receptor antagonist, SR49059, reduces brain edema by modulating AQP4 expression following cortical contusion injury (CCI).

Methods Traumatic brain injury (TBI) was produced in thirty-two adult male Sprague-Dawley rats by lateral CCI (6.0 m/sec, 3 mm depth). Animals were randomly assigned to vehicle (n=16) or SR49059 treatment (n=16) groups and administered drug (960 μl/hr i.v.) immediately after injury over a 5 hr period. Animals were sacrificed for assessment of brain water content by Wet/Dry method and AQP4 protein expression by immunoblotting expressed as the ratio of AQP4 and Cyclophilin-A densitometries.

Findings Elevated AQP4 expression levels and water content were observed on the right injured side in both the right anterior (RA) and right posterior (RP) section compared to the left non-injured side inclusive of the left anterior (LA) and right anterior (RA) sections. The average AQP4 expression levels in contused areas for animals receiving SR drug treatment (RA: 1.313±0.172, RP: 1.308± 0.175) were significantly decreased from vehicle-treated animals (RA: 2.181±0.232, RP: 2.303±0.370, p=0.001, p= 0.003). Water content levels on SR treatment (78.89±0.14) was also significantly decreased from vehicle levels (80.38± 0.38, p<0.01) in the traumatized hemisphere.

Conclusions SR49059 significantly reduced trauma-induced AQP4 up-regulation in the contused hemisphere. Moreover, brain water content was also significantly reduced paralleling the AQP4 suppression. These data provide further support that vasopressin (AVP) and V1a receptors can control water flux through astrocytic plasma membranes by regulating AQP4 expression. Taken in concert, these results affirm our laboratories contention that AQP4 can be effectively modulated pharmacologically.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agre P, Kozono D (2003) Aquaporin water channels: molecular mechanisms for human deseases. FEBS Lett 555:72–78

    Article  PubMed  CAS  Google Scholar 

  2. Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nat Rev Neurosci 4:991–1001

    Article  PubMed  CAS  Google Scholar 

  3. Bemana I, Nagao S (1999) Treatment of brain edema with a nonpeptide arginine vasopressin V1 receptor antagonist OPC-21268 in rats. Neurosurgery 44:148–155

    Article  PubMed  CAS  Google Scholar 

  4. Buijs RM (1978) Intra and extrahypothalamic vasopressin and oxytocin pathway in the rat. Pathways to limbic system, medulla oblongata and spinal cord. Cell Tissue Res 192:423–435

    Article  PubMed  CAS  Google Scholar 

  5. Chen Y, McNeill JR, Hajek I, Hertz L (1992) Effect of vasopressin on brain swelling at the cellular level: do astrocytes exhibit a furosemide-vasopressin-sensitive mechanism for volume regulation? Can J Physiol Pharmacol 70:S367–S373

    PubMed  CAS  Google Scholar 

  6. Cserr HF, Latzkovits L (1992) A role for centrally released vasopressin in brain ion and volume regulation: a hypothesis. Prog Brain Res 91:3–6

    Article  PubMed  CAS  Google Scholar 

  7. Del Bigio MR, Fedoroff S (1990) Swelling of astroglia in vitro and the effect of arginine vasopressin and atrial natriuretic peptide. Acta Neurochir Suppl 51:14–16

    Google Scholar 

  8. DePasquale M, Patlak CS, Cserr HF (1989) Brain ion and volume regulation during acute hypernatremia in Brattleboro rats. Am J Physiol 256:F1059–F1066

    Google Scholar 

  9. de Vries GJ, Miller MA (1998) Anatomy and function of extrahypothalamic vasopressin systems in the brain. Prog Brain Res 199:3–20

    Google Scholar 

  10. Dickinson LD, Betz AL (1992) Attenuated development of ischemic brain edema in vasopressin deficient rats. J Cereb Blood Flow Metab 12:681–690

    PubMed  CAS  Google Scholar 

  11. Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL (1991) A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods 39:253–262

    Article  PubMed  CAS  Google Scholar 

  12. Doczi T, Szerdahelyi P, Gluya K, Kiss J (1982) Brain water accumulation after the central administration of vasopressin. Neurosurgery 11:402–407

    PubMed  CAS  Google Scholar 

  13. Doczi T, Laszlo FA, Szerdahelyi P, Joo F (1984) Involvement of vasopressin in brain edema formation: further evidence obtained from the Brattleboro diabetes insipidus rat with experimental subarachnoid hemorrhage. Neurosurgery 14:436–441

    Article  PubMed  CAS  Google Scholar 

  14. Faraci FM, Mayhan WG, Farrrell WJ, Heistad DD (1988) Humoral regulation of blood flow to choroid plexus: role of arginine vasopressin. Circ Res 63:373–379

    PubMed  CAS  Google Scholar 

  15. Finkelstein A (1987) Water movements through lipid bilayers, pores and plasma membranes: theory and reality. John Wiley & Sons, New York

    Google Scholar 

  16. Graham DI, Adams JH, Nicoll JA, Maxwell WL, Gennarelli TA (1995) The nature, distribution and causes of traumatic brain injury. Brain Pathol 5:397–406

    Article  PubMed  CAS  Google Scholar 

  17. Kleindienst A, Fazzina G, Dunbar JG, Glisson R, Marmarou A (2006) Protective effect of the V1a receptor antagonist SR49059 on brain edema formation following middle cerebral artery occlusion in the rat. Acta Neurochir Suppl 96:303–306

    Article  PubMed  CAS  Google Scholar 

  18. Landgraf R (1992) Central release of vasopressin: stimuli, dynamics, consequences. Prog Brain Res 91:29–39

    Article  PubMed  CAS  Google Scholar 

  19. Latzkovits L, Cserr HF, Park JT, Patlak CS, Pettigrew KD, Rimanoczy A (1993) Effects of arginine vasopressin and atriopeptin on glial cell volume measured as 3-MG space. Am J Physiol 264:C603–C608

    PubMed  CAS  Google Scholar 

  20. Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6:159–163

    Article  PubMed  CAS  Google Scholar 

  21. Marmarou A (1994) Traumatic brain edema: an overview. Acta Neurochir Suppl 60:421–424

    CAS  Google Scholar 

  22. Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP (1997) Specialized membrane domains for water transport in glial cells: high- resolution immunogold cytochemistry of aquaporin4 in rat brain. J Neurosci 17:171–180

    PubMed  CAS  Google Scholar 

  23. Nierman H, Amry-Moghaddam M, Holthoff K, Witte Ow, Ottersen OP (2001) A novel role of vasopressin in the brain: modulation of activity-dependent water flux in the neocortex. J Neurosci 21:3045–3051

    Google Scholar 

  24. Noto T, Nakajima T, Saji Y, Nagawa Y (1978) Effect of vasopressin on intracranial pressure of rabbit. Endocrinol Jpn 25:591–596

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  26. Raichle ME, Grubb RL (1978) Regulation of brain water permeability by centrally released vasopressin. Brain Res 143: 191–194

    Article  PubMed  CAS  Google Scholar 

  27. Reeder RF, Nattie EE, North WG (1986) Effect of vasopressin on cold-induced brain edema in cats. J Neurosurg 64:941–950

    Article  PubMed  CAS  Google Scholar 

  28. Rosenberg GA, Scremin O, Estrada E, Keyner WT (1992) Arginine vasopressin V1 antagonist and atrial natriuretic peptide reduce hemorrhagic brain edema in rats. Stroke 23:1767–1774

    PubMed  CAS  Google Scholar 

  29. Serradeil-Le Gal C, Wagnon J, Garcia C, Lacour C, Guiraudou P, Christophe B, Villanova G, Nisato D, Maffrand JP, Fur GL, Guillon G, Cantau B, Barberies C, Trueba M, Ala Y, Jard S (1993) Biochemical and pharmacological properties of SR49059, a new, potent, nonpeptide antagonist of rat and human vasopressin V1a receptors. J Clin Invest 92:224–231

    Article  PubMed  CAS  Google Scholar 

  30. Shuaib A, Wang CX, Yang T, Noor R (2002) Effects of nonpeptide V1 vasopressin receptor antagonist SR49059 on infarction volume and recovery of function in a focal embolic stroke model. Stroke 33:3033–3037

    Article  PubMed  CAS  Google Scholar 

  31. Thibonnier M, Kilani A, Rahman M, DiBlasi TP, Warner K, Smith MC, Leenhardt AF, Brouard R (1999) Effects of the nonpeptide V1 vasopressin receptor antagonist SR49059 in hypertensive patients. Hypertension 34:1293–1300

    PubMed  CAS  Google Scholar 

  32. Tribollet E, Raufaste D, Maffrand JP, Serradeil-Le Gal C (1999) Binding of the non-peptide vasopressin V1a receptor antagonist SR49059 in te rat brain: an in vitro and in vivo autoradiographic study. Neuroendocrinology 69:113–120

    Article  PubMed  CAS  Google Scholar 

  33. Venero JL, Vizuete ML, Machado A, Cano J (2001) Aquaporins in the central nervous system. Prog Neurobiol 63:321–336

    Article  PubMed  CAS  Google Scholar 

  34. Verkman AS (2002) Physiological importance of aquaporin water channels. Ann Med 34:192–200

    Article  PubMed  CAS  Google Scholar 

  35. Zeuthen T (1994) Cotransport of K+,Cl− and H2O by membrane proteins from choroid plexus epithelium of Necturus maculosus. J Physiol 478:203–219

    PubMed  CAS  Google Scholar 

  36. Zeuthen T, Meinild AK, Klaerke DA, Loo DD, Wright EM, Belhage B, Litman T (1997) Water transport by the Na+/ glucose cotrans porter under isotonic conditions. Biol Cell 89:307–312

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Virginia Commonwealth University Medical Center, 1101 East Marshall Street, 980508, Richmond, VA, 23298-0508, USA

    Keisuke Taya, Salih Gulsen, Kenji Okuno, Ruth Prieto, Christina R. Marmarou & Anthony Marmarou

  2. Baskent Universitesi Tip Fakultesi Hastanesi, Beyin Cerrahisi Bolumu, Bahcelievler, Ankara, 06490, Turkey

    Salih Gulsen

  3. Department of Neurosurgery, Clínico San Carlos University Hospital Planta Sexta — Ala Sur, Profesor Martin Lagos s/n, Madrid, Madrid, 28040, Spain

    Ruth Prieto

  4. Department of Emergency Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi Minato-ku, Tokyo, 105-8461, Japan

    Kenji Okuno

Authors
  1. Keisuke Taya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Salih Gulsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenji Okuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruth Prieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christina R. Marmarou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anthony Marmarou
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

H. -J. Steiger

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag/Wien

About this paper

Cite this paper

Taya, K., Gulsen, S., Okuno, K., Prieto, R., Marmarou, C.R., Marmarou, A. (2008). Modulation of AQP4 expression by the selective V1a receptor antagonist, SR49059, decreases trauma-induced brain edema. In: Steiger, H.J. (eds) Acta Neurochirurgica Supplements. Acta Neurochirurgica Supplementum, vol 102. Springer, Vienna. https://doi.org/10.1007/978-3-211-85578-2_83

Download citation

  • DOI: https://doi.org/10.1007/978-3-211-85578-2_83

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-85577-5

  • Online ISBN: 978-3-211-85578-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation