Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window.

Abstract

We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection. Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-L-lysine-coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined. Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67% and 58%, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68%), subcortical regions (by 52%), and total infarct (by 61%). Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.