Tissue plasminogen activator and glial function

Tissue plasminogen activator (tPA) is the only FDA-approved treatment of thrombotic stroke and is a major parenchymal serine protease in the brain. However, it has been implicated in a plethora of brain pathologies, raising concern about its use as a safe therapeutic. tPA is thought to regulate physiological processes that entail tissue remodeling and plasticity, purportedly due to its ability to initiate the degradation of extracellular matrix proteins and possibly other substrates. Understanding the physiological role(s) of tPA promises to both elucidate important aspects of brain function and improve the available therapies for neurological disease. In this context, the effects of tPA on glial cells, mainly microglial cells, but also astrocytes and Schwann cells, appear to be of particular importance, given the increasing awareness of the significance of glia in brain physiology and pathology.