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

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Acta Neurochirurgica Supplements

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

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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.

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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

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  1. Keisuke Taya
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  5. Christina R. Marmarou
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H. -J. Steiger

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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

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

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