Summary
There exists no pharmacological treatment for fulminating brain edema. Since evidence indicates that brain aquaporin-4 (AQP4) water channels are modulated by vasopressin V1a receptors, we examined the edema-reducing properties of the selective V1a receptor antagonist, SR49059, following middle cerebral artery occlusion (MCAO).
Male Sprague-Dawley rats were randomly assigned to sham procedure, vehicle, or SR49059 infusion at different dosages (each n = 6, 480 μL/hr, 640 μL/hr, 720 μL/hr) and starting 60 minutes before or after MCAO. After a 2-hour period of ischemia and 2 hours of reperfusion, the animals were sacrificed for assessment of brain water content, sodium, and potassium concentration. Statistics were performed using an ANOVA followed by a Tukey post hoc analysis.
SR049059 treatment reduced brain water content in the infarcted area given at 640 μL/hr (p = 0.036), 720 μL/hr 60 minutes before (p = 0.002) or 60 minutes after (p = 0.005) MCAO. The consecutive sodium shift into the brain was prevented (p = 0.001), while the potassium loss was inhibited only by pre-treatment (p = 0.003).
These findings imply that in ischemia-induced brain edema, the selective V1a receptor-antagonist SR49059 inhibits brain edema and the subsequent sodium shift into brain. This substance offers a new avenue in brain edema treatment and prompts further study into AQP4 modulation.
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Kleindienst, A., Fazzina, G., Dunbar, J.G., 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. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_65
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DOI: https://doi.org/10.1007/3-211-30714-1_65
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