Intravenously administered recombinant tissue-plasminogen activator attenuates neuronal injury after mild focal cerebral ischemia in mice.
Recombinant tissue-plasminogen activator (t-PA) increases brain injury after focal ischemias leading to overt tissue infarcts. The question arose, whether t-PA may also be detrimental after mild ischemias. To clarify this issue, we submitted mice to 30 min intraluminal thread occlusions and administered normal saline or t-PA (10 mg/kg, i.v.) after reperfusion onset. Thread occlusions resulted in reproducible ischemias, followed by hyperperfusion reactions immediately after thread withdrawal. Post-ischemic LDF did not differ between saline- and t-PA-treated animals. In contrast to earlier studies, where t-PA exacerbated injury, t-PA treatment did not increase, but attenuated disseminate neuronal death in the striatum, as shown by cresyl violet, TUNEL and activated caspase-3 staining 1 and 3 days after the ischemic event (p < 0.05). Our data argue against major detrimental actions of t-PA after mild focal ischemia.
Kilic
Ertugrul
E
Department of Neurology, University Hospital Zürich, Frauenklinikstr. 26, CH-8091 Zürich, Switzerland. ertugrul.kilic@usz.ch
Kilic
Ulkan
U
Bassetti
Claudio L
CL
Hermann
Dirk M
DM
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002544:Cerebral Infarction / Q000378:metabolism / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004195:Disease Models, Animal; D018450:Disease Progression; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D010959:Tissue Plasminogen Activator; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases