title: Erythrocyte-bound tissue plasminogen activator is neuroprotective in experimental traumatic brain injury.
abstract: The purpose of this study was to test the effects of exogenous tissue plasminogen activator (tPA) in traumatic brain injury (TBI).We tested two different tPA formulations, free tPA and tPA bound to erythrocytes (RBC/tPA).Vehicle and each of the tPA treatments were injected intravenously into anesthetized rats 15 min after moderate lateral fluid percussion injury. The animals were sacrificed at 2 days for calculating microclot burden (n=13) and IgG staining area (n=13) in the brain sections as indicators of post-traumatic thrombosis and blood-brain barrier (BBB) breakdown, respectively. Another set of injured animals treated in the same way were sacrificed at 7 days to compare cortical lesion volumes (n=28) and CA3 hippocampal cell loss (n=24). All evaluations were done blinded with respect to treatment. No significant differences were found with respect to microclot burden or IgG staining volume. Injection of wild-type tPA caused significantly ( p<0.05) larger cortical injuries and greater cerebral hemorrhage. In contrast, there was significantly less cortical injury ( p<0.01) and hippocampal cell loss ( p<0.01) in the RBC=tPA group than in all other groups. These results reveal that RBC/tPA is more neuroprotective in experimental TBI than is unbound tPA.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19106, USA. sherman.stein@uphs.upenn.edu
authors.forename: Sherman C
authors.initials: SC
authors.lastname: Stein
authors.forename: Kumkum
authors.initials: K
authors.lastname: Ganguly
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Belfield
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Xu
authors.forename: Edward W
authors.initials: EW
authors.lastname: Swanson
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Chen
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Browne
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Johnson
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
authors.forename: David G
authors.initials: DG
authors.lastname: LeBold
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cines
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykantov
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykhantov