effects of estradiol on ischemic factorinduced astrocyte swelling and aqp4 protein abundance in the early hours of ischemic stroke cerebral edema forms as na cl and water are secreted across the bloodbrain barrier bbb and astrocytes swell we have shown previously that ischemic factors including hypoxia aglycemia and arginine vasopressin avp stimulate bbb nakcl cotransporter nkcc and nah exchanger nhe activities and that inhibiting nkcc andor nhe by intravenous bumetanide andor hoe642 reduces edema and infarct in a rat model of ischemic stroke estradiol also reduces edema and infarct in this model and abolishes ischemic factor stimulation of bbb nkcc and nhe there is evidence that nkcc and nhe also participate in ischemiainduced swelling of astrocytes however little is known about estradiol effects on astrocyte cell volume in this study we evaluated the effects of avp 100 nm hypoxia 75 o2 aglycemia hypoxia 2aglycemia oxygen glucose deprivation ogd and estradiol 1100 nm on astrocyte cell volume using 3omethyld3hglucose equilibration methods we found that avp hypoxia aglycemia and ogd 30 min to 5 h each significantly increased astrocyte cell volume and that estradiol 30180 min abolished swelling induced by avp or hypoxia but not by aglycemia or ogd bumetanide andor hoe642 also abolished swelling induced by avp but not aglycemia abundance of aquaporin4 known to participate in ischemiainduced astrocyte swelling was significantly reduced following 7day but not 2 or 3h estradiol exposures our findings suggest that hypoxia aglycemia and avp each contribute to ischemiainduced astrocyte swelling and that the edemaattenuating effects of estradiol include reduction of hypoxia and avpinduced astrocyte swelling and also reduction of aquaporin4 abundance