Albumin ameliorates tissue plasminogen activator-mediated blood-brain barrier permeability and ischemic brain injury in rats

Objective: Tissue plasminogen activator (tPA) may aggravate ischemic neuronal damage after focal cerebral ischemia and increase blood-brain barrier permeability. Human serum albumin has neuroprotective effects on ischemic stroke. However, whether albumin can attenuate the deleterious effects of tPA is yet unknown. Methods: In the present study, we attempted to determine the effects of albumin on cerebral injury and blood-brain barrier disruption induced by middle cerebral artery occlusion for 2 hours followed by 24 hours of reperfusion and tPA. Results: We found that infarct volume in rats which received saline and tPA was 35.6 +/- 3.8% (mean +/- SEM) and 50.9 +/- 4.5%, respectively. There was significant difference between the two groups (p<0.01). The infarct volume in rats that received tPA with albumin was significantly decreased to 29.2 +/- 3.3% (p<0.05), compared with tPA-only-treated group. Combination therapy using tPA with albumin also improved neurological deficits and reduced brain edema significantly (p<0.05). Relative to tPA-treated group, rats that received combination therapy using tPA with albumin had significantly reduced blood-brain barrier permeability, evaluated by quantitation of Evans blue leakage (p<0.05). Conclusion: In acute ischemic stroke, combination therapy using tPA with albumin can attenuate the deleterious effects of tPA. [Neurol Res 2009; 31: 189-194]