Tissue Plasminogen Activator (tPA) Promotes Postnatal Cortical Neuron Survival in Vitro Via JAK2- and mTOR-Dependent Mechanisms
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Tissue plasminogen activator (tPA) is the only approved drug for ischemic stroke in Canada but is limited in its clinical efficacy due to its short therapeutic window. This study sought to determine the effect of tPA on postnatal primary cortical neuron viability and aimed to identify the relevant cellular signalling mechanisms underlying the tPA-mediated effects in vitro. The data revealed that tPA significantly increased the propensity for cell survival within a time latency window of up to 3 hours. tPA-induced neuroprotective effects were significantly dependent upon the mTOR and JAK/STAT signalling pathways, while the MEK and PKA signalling pathways were found to play a less critical role. Immunocytochemical staining showed a marked increase in p-S6 expression following treatment with tPA, substantiating the vital role of mTOR activation in tPA-mediated neuroprotection. These results suggest the possibility of targeting the defined mechanisms to expand the therapeutic window of tPA in stroke recovery.
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Copyright © 2015 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
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grummisch-tissueplasminogenactivatortpapromotespostnatal.pdf | 2023-05-04 | Public | Download |