Anti‐tissue Plasminogen Activator (tPA) as an Effective Therapy of Neonatal Hypoxia–Ischemia with and without Inflammation

Summary Hypoxic–ischemic brain injury is an important cause of neurodevelopmental deficits in neonates. Intrauterine infection and the ensuing fetal inflammatory responses augment hypoxic–ischemic brain injury and attenuate the efficacy of therapeutic hypothermia. Here, we review evidences from preclinical studies suggesting that the induction of brain parenchymal tissue‐type plasminogen activator (t PA ) plays an important pathogenic role in these conditions. Moreover, administration of a stable‐mutant form of plasminogen activator inhibitor‐1 called CPAI confers potent protection against hypoxic–ischemic injury with and without inflammation via different mechanisms. Besides intracerebroventricular injection, CPAI can also be administered into the brain using a noninvasive intranasal delivery strategy, adding to its applicability in clinical use. In sum, the therapeutic potential of CPAI in neonatal care merits further investigation with large‐animal models of hypoxia–ischemia and cerebral palsy.