Albumin reduces blood-brain barrier permeability but does not alter infarct size in a rat model of neonatal stroke.

Human serum albumin therapy confers neurobehavioral and histopathologic neuroprotection in adult stroke models. We investigated whether albumin might also be neuroprotective in ischemic brain injury using a transient filament middle cerebral artery occlusion (tfMCAO) model in 10-d-old rat pups treated with 0.25% albumin or saline 1 h after reperfusion. We performed serial neurobehavioral and magnetic resonance imaging (MRI) assessments immediately after tfMCAO (day 0) and on 1, 3, 7, 14, and 28 d. IgG staining to assess blood-brain barrier (BBB) integrity and standard histology was obtained on 1, 3, and 28 d. Hemispheric infarct volumes from MRI were similar in saline and albumin groups (0 h: 39% and 44%; d 1: 46% and 55%; and d 28:10% and 24%) as were neurobehavioral assessments. IgG staining at 3 d post-ischemia showed loss of BBB integrity that was significantly reduced after albumin. Elevated T2 values suggesting vasogenic edema was seen in albumin compared with saline-treated animals, as was increased water mobility (i.e. increased apparent diffusion coefficient (ADC) reflecting cytotoxic edema. The reasons why albumin was not neuroprotective in neonatal stroke compared with adults remain uncertain. Effective strategies in adult models need to be reassessed in the neonate.