Reduced cortical injury and edema in tissue plasminogen activator knockout mice after brain trauma.
Tissue plasminogen activator (tPA) may play a deleterious role after brain injury. Here, we compared the response to traumatic brain injury in tPA knockout (KO) and wildtype (WT) mice after controlled cortical impact. At 6 h after trauma, blood-brain barrier permeability was equally increased in all mice. However, by 24 h specific gravity measurements of brain edema were significantly worse in WT mice than in KO mice. At 1 and 2 days post-trauma, mice showed deficits in rotarod performance, but by day 7 all mice recovered motor function and there were no differences between WT and KO mice. At 7 days, cortical lesion volumes were significantly reduced in KO mice compared with WT mice. However, there were no significant differences in CA3 hippocampal neuron survival. These data suggest that tPA amplifies cortical brain damage and edema in this mouse model of traumatic brain injury.
Mori
T
T
Neuroprotection Research Laboratory, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, MGH East 149-2322, Charlestown, MA 02129, USA.
Wang
X
X
Kline
A E
AE
Siao
C J
CJ
Dixon
C E
CE
Tsirka
S E
SE
Lo
E H
EH
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000293:injuries* / Q000473:pathology; D004396:Coloring Agents / Q000493:pharmacokinetics; D005070:Evans Blue / Q000493:pharmacokinetics; D005109:Extracellular Matrix / Q000502:physiology; D006624:Hippocampus / Q000098:blood supply / Q000293:injuries / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009474:Neurons / Q000473:pathology; D020127:Recovery of Function; D010959:Tissue Plasminogen Activator / Q000235:genetics*
D004396:Coloring Agents; D005070:Evans Blue; D010959:Tissue Plasminogen Activator