This disclosure relates to managing brain injury. In certain embodiments, this disclosure relates to methods comprising administering an effective amount of an inhibitor of sphingosine-1-phoshate signaling, an inhibitor of retinoic-acid-receptor-related orphan receptors α or γ, and/or an inhibitor of tPA microglial activation to a subject in need thereof. Typically, the subject is a neonate or a neonate born prematurely.
