Application of albumin prior to delayed thrombolysis reduces brain edema and blood brain barrier permeability in an embolic stroke model

To explore whether human albumin (Alb) administration prior to thrombolysis with recombinant tissue plasminogen activator (rt-PA) can eliminate brain damage induced by this treatment given after the effective and safe window of 3 h after stroke onset. Rats were subjected to embolic stroke by unilateral embolic middle cerebral artery occlusion (MCAO). Three or six hours after the onset of stroke, rats were administered intravenously with saline (control), rt-PA (thrombolysis) or rt-PA + Alb (additional Alb 3 h after MCAO, combination). Cerebral blood flow, infarct volume, space-occupying effect and blood brain barrier (BBB) leakage of gadopentetate dimeglumine (Gd-DTPA) were assessed dynamically by magnetic resonance imaging (MRI) at 24 h, 7 and 14 days after treatment. BBB leakage of both fluoro-isothiocyanate dextran (FITC-dextran) and erythrocytes was also evaluated 14 days after treatment. The space-occupying effect in the combination group at 7 days after treatment declined significantly compared with that at 24 h after treatment (P < 0.05), but additional Alb treatment failed to reduce the infarct volumes or improve cerebral blood volume. Furthermore, BBB leakage of both small (Gd-DTPA) and large (FITC-dextran and erythrocytes) molecules decreased significantly in the combination compared to the saline or thrombolysis groups (P < 0.05). Alb administration prior to thrombolysis (3 h after stroke) can reduce delayed rt-PA treatment-induced brain edema and BBB permeability.