Protease-independent action of tissue plasminogen activator in brain plasticity and neurological recovery after ischemic stroke.

ABSTRACT: Emerging evidence suggests that tissue plasminogen activator (tPA), currently the only FDA-approved medication for ischemic stroke, exerts important biological actions on the CNS besides its well-known thrombolytic effect. In this study, we investigated the role of tPA on primary neurons in culture and on brain recovery and plasticity after ischemic stroke in mice. Treatment with recombinant tPA stimulated axonal growth in culture, an effect independent of its protease activity and achieved through epidermal growth factor receptor (EGFR) signaling. After permanent focal cerebral ischemia, tPA knockout mice developed more severe sensorimotor and cognitive deficits and greater axonal and myelin injury than wild-type mice, suggesting that endogenously expressed tPA promotes long-term neurolog

SUBMITTER: Pu H 

PROVIDER: S-EPMC6500126 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature