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Pregnancy-induced up-regulation of aquaporin-4 protein in brain and its role in eclampsia

Departments of Neurology, Pharmacology and Ob/Gyn, University of Vermont College of Medicine, Burlington, Vermont, USA

¹Correspondence: University of Vermont College of Medicine, Department of Neurology, 89 Beaumont Ave., Given C454, Burlington, VT 05405, USA. E-mail: Marilyn.Cipolla{at}uvm.edu

Neurologic complications of eclampsia are thought to be similar to hypertensive encephalopathy in which an acute, excessive elevation in blood pressure causes blood-brain barrier (BBB) disruption and edema formation. Because women who develop eclampsia are in general normotensive and asymptomatic prior to pregnancy, we hypothesized that pregnancy alone predisposes the brain to edema formation by up-regulation of aquaporin 4 (AQP4), a water channel in the brain that has been shown to positively correlate with edema formation. To test this hypothesis, we compared localization (immunohistochemistry), mRNA (RT-PCR), and protein levels (Western analysis) of AQP4 in brains from Sprague Dawley rats that were nonpregnant (NP, proestrous), mid-pregnant (MP, days 9–10), late-pregnant (LP, days 19–20), and postpartum (PP, days 3–4). AQP4 mRNA was detected in the brains of all the animals and was localized primarily around the brain parenchymal blood vessels, strongly implicating its role in BBB function. Western analysis revealed that the major AQP4 band at 32 kDa was significantly elevated in MP, LP, and PP animals compared with NP by 9-, 22-, and 17-fold, respectively. These results suggest that pregnancy and the postpartum state up-regulate AQP4 protein located around the intraparenchymal blood vessels, a consequence that could promote edema formation when blood pressure is acutely and excessively elevated, as during eclampsia.—Quick, A. M., Cipolla, M. J. Pregnancy-induced up-regulation of aquaporin-4 protein in brain and its role in eclampsia.

Key Words: aquaporins • blood-brain barrier • AQP4 protein expression

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