Tissue-type plasminogen activator is involved in the process of neuronal death induced by oxygen-glucose deprivation in culture

Effect of tissue-type plasminogen activator (tPA) on oxygen-glucose depriva tion (OGD) was studied in cultured cortical neurons prepared from tPA gene knockout (tPA-KO) and wild-type (Wt) mice. Three hours of OGD induced 45% a nd 23% of neuronal death in Wt and tPA-KO mice, respectively. Neuronal deat h in tPA-KO mice was increased to 42% by additional tPA. Six hours of OGD i nduced 80% and 40% of neuronal death in Wt and tPA-KO mice, respectively. w hereas the addition of tPA increased to 62% in tPA-KO mice. These results s uggest that tPA is directly involved in the process of neuronal death induc ed by ischemia-mimic stress without involving vascular or circulatory compo nents.