Thrombolysis with tissue plasminogen activator alters adhesion molecule expression in the ischemic rat brain

Background and Purpose-We tested the hypothesis that treatment of embolic s troke with recombinant human tissue plasminogen activator (rhtPA) alters ce rebral expression of adhesion molecules. Methods-Male Wistar rats were subjected to middle cerebral artery occlusion by a single fibrin-rich clot. P-selectin, E-selectin, and intercellular ad hesion molecule-1 (ICAM-1) immunoreactivity was measured at 6 or 24 hours a fter embolic stroke in control rats and in rats treated with rhtPA at 1 or 4 hours after stroke. To examine the therapeutic efficacy of combined rhtPA and anti-ICAM-1 antibody treatment at 4 hours after embolization, ischemic lesion volumes were measured in rats treated with rhtPA alone, rats treate d with rhtPA and anti-ICAM-1 antibody, and nontreated rats. Results-Administration of rhtPA at 1 hour after embolization resulted in a significant reduction of adhesion molecule vascular immunoreactivity after embolization in the ipsilateral hemisphere compared with corresponding cont rol rats. However, when rhtPA was administered to rats at 4 hours after emb olization, significant increases of adhesion molecule immunoreactivity in t he ipsilateral hemisphere were detected. A significant increase of ICAM-1 i mmunoreactivity was also detected in the contralateral hemisphere at 24 hou rs after ischemia. A significant reduction in lesion volume was found in ra ts treated with the combination of rhtPA and anti-ICAM-1 antibody compared with rats treated only with rhtPA. Conclusions-The present study suggests that the time of initiation of throm bolytic therapy alters vascular immunoreactivity of inflammatory adhesion m olecules in the ischemic brain and that therapeutic benefit can be obtained by combining rhtPA and anti-ICAM-1 antibody treatment 4 hours after stroke .