title: Early (1 h) administration of tissue plasminogen activator reduces infarct volume without increasing hemorrhagic transformation after focal cerebral embolization in rats.
abstract: 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.
authors.affiliation: Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Chopp
authors.forename: Z G
authors.initials: ZG
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Divine
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002544:Cerebral Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D011993:Recombinant Fusion Proteins; D010959:Tissue Plasminogen Activator