Early (1 h) administration of tissue plasminogen activator reduces infarct volume without increasing hemorrhagic transformation after focal cerebral embolization in rats

We assessed the incidence of hemorrhagic transformation and infarct volume after early intravenous infusion of recombinant human tissue plasminogen activator (rht-PA) in a newly developed rat cerebral embolic model. Male Wistar rats (n=60) were subjected to middle cerebral artery (MCA) occlusion by a single fibrin rich clot. One hour after embolization, rats were assigned to the following groups: (1) rht-PA treated group (n=20); (2) vehicle treated group (n=20); and (3) saline treated group (n=20). Neurological deficits, lodgement of a clot at the origin of the MCA, infarction volume and microscopic hemorrhage were measured. Animals exhibited moderate to severe neurological deficits 1 h after MCA occlusion in all groups. Administration of rht-PA significantly (P<0.05) reduced the incidence of lodgement of a clot at the origin of the MCA (30%) compared with the saline treated group (100%) and the vehicle treated group (80%). A significant (P<0.05) reduction of percent hemispheric infarct volume was detected between the saline (33.2+/-3.71%) and the rht-PA groups (19.4+/-3.3%). However, no significant difference was found in the total area of microscopic hemorrhage of the rht-PA (0.05+/-0.02 mm2), the vehicle (0.02+/-0.01 mm2), and the saline (0.03+/-0.02 mm2) treated groups. No significant difference of percent hemispheric infarct volume (P=0.08) was observed between the vehicle and the rht-PA treated groups. This study demonstrates that treatment with rht-PA reduced infarct volume without increasing intracerebral hemorrhage in rats with large cerebral infarction when treatment was initiated at 1 h of the onset of embolization.