biostudies-literatureThiebaut AMSwiss National Science Foundation1297-1317https://www.ebi.ac.uk/biostudies/studies/S-EPMC9225202biostudies-literatureUnknown18(6)Cerebral ischemia is a pathology involving a cascade of cellular mechanisms, leading to the deregulation of proteostasis, including macroautophagy/autophagy, and finally to neuronal death. If it is now accepted that cerebral ischemia induces autophagy, the effect of thrombolysis/energy recovery on proteostasis remains unknown. Here, we investigated the effect of thrombolysis by PLAT/tPA (plasminogen activator, tissue) on autophagy and neuronal death. In two <i>in vitro</i> models of hypoxia reperfusion and an <i>in vivo</i> model of thromboembolic stroke with thrombolysis by PLAT/tPA, we found that ischemia enhances neuronal deleterious autophagy. Interestingly, PLAT/tPA decreases autophagy to mediate neuroprotection by modulating the PI3K-AKT-MTOR pathways both <i>in vitro</i> and <i>in vAutophagyThrombolysis by PLAT/tPA increases serum free IGF1 leading to a decrease of deleterious autophagy following brain ischemia.PMC9225202310030182332163064Buendia ILebouvier LRoussel BDOury FThiebaut AMLemarchand EMaillasson MRubio MBoudjadja MBGinet VVivien DHommet YMontaner JLechevallier CPuyal JHedou EDeglon NfalseThrombolysis by PLAT/tPA increases serum free IGF1 leading to a decrease of deleterious autophagy following brain ischemia.Cerebral ischemia is a pathology involving a cascade of cellular mechanisms, leading to the deregulation of proteostasis, including macroautophagy/autophagy, and finally to neuronal death. If it is now accepted that cerebral ischemia induces autophagy, the effect of thrombolysis/energy recovery on proteostasis remains unknown. Here, we investigated the effect of thrombolysis by PLAT/tPA (plasminogen activator, tissue) on autophagy and neuronal death. In two <i>in vitro</i> models of hypoxia reperfusion and an <i>in vivo</i> model of thromboembolic stroke with thrombolysis by PLAT/tPA, we found that ischemia enhances neuronal deleterious autophagy. Interestingly, PLAT/tPA decreases autophagy to mediate neuroprotection by modulating the PI3K-AKT-MTOR pathways both <i>in vitro</i> and <i>in v2022-01-01T00:00:00Z2022 Jun2026-05-09T16:18:22.137Z2024-11-21T01:23:34.104ZS-EPMC92252023452033410.1080/15548627.2021.1973339