title: Magnesium sulphate treatment decreases blood-brain barrier permeability during acute hypertension in pregnant rats.
abstract: Eclampsia is associated with increased blood-brain barrier (BBB) permeability and formation of cerebral oedema. Magnesium sulphate is used to treat eclampsia despite an unclear mechanism of action. This study was to determine the effect of magnesium sulphate on in vivo BBB permeability and formation of cerebral oedema during acute hypertension and on brain aquaporin-4 (AQP4) protein expression. An in vivo model of hypertensive encephalopathy was used in late-pregnant (LP) rats following magnesium sulphate treatment, 270 mg kg(-1) i.p. injection every 4 h for 24 h. Permeability of the BBB was determined by in situ brain perfusion of Evan's Blue (EB) and sodium fluorescein (NaFl), and dye clearance determined by fluorescence spectrophotometry. Cerebral oedema was determined following acute hypertension by measuring brain water content. The effect of magnesium treatment on AQP4 expression was determined by Western blot analysis. Acute hypertension with autoregulatory breakthrough increased BBB permeability to EB in both brain regions studied (P < 0.05). Magnesium attenuated BBB permeability to EB during acute hypertension by 41% in the posterior cerebrum (P < 0.05) but had no effect in the anterior cerebrum (P > 0.05). Treatment with magnesium did not change NaFl permeability, cerebral oedema formation or AQP4 expression. In summary, BBB permeability to Evan's Blue was increased by acute hypertension in LP rats, and this was attenuated by treatment with magnesium sulphate. The greatest effect on BBB permeability to EB was in the posterior cerebrum, an area particularly susceptible to oedema formation during eclampsia.
authors.affiliation: University of Vermont, Department of Neurology, 89 Beaumont Avenue, Given C454, Burlington, VT 05405, USA.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Euser
authors.forename: Lisa
authors.initials: L
authors.lastname: Bullinger
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Cipolla
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000096:biosynthesis; D001812:Blood-Brain Barrier / Q000187:drug effects*; D015153:Blotting, Western; D001834:Body Water / Q000502:physiology; D001929:Brain Edema / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004396:Coloring Agents; D005070:Evans Blue; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D046110:Hypertension, Pregnancy-Induced / Q000378:metabolism*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D010539:Permeability; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051401:Aquaporin 4; D004396:Coloring Agents; D005070:Evans Blue; D008278:Magnesium Sulfate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases