Regeneration using endogenous neural stem cells following neonatal brain injury

Abstract

Despite recent advancements in perinatal care, the incidence of neonatal brain injury has not decreased. No therapies are currently available to repair injured brain tissues. In the postnatal brain, neural stem cells reside in the ventricular-subventricular zone (V-SVZ) and continuously generate new immature neurons (neuroblasts). After brain injury in rodents, V-SVZ-derived neuroblasts migrate toward the injured area using blood vessels as a scaffold. Notably, the neonatal V-SVZ has a remarkable neurogenic capacity. Furthermore, compared with the adult brain, after neonatal brain injury, larger numbers of neuroblasts migrate toward the lesion, raising the possibility that the V-SVZ could be a source for endogenous neuronal regeneration after neonatal brain injury. We recently demonstrated that efficient migration of V-SVZ-derived neuroblasts toward a lesion is supported by neonatal radial glia via neural cadherin (N-cadherin)-mediated neuron-fiber contact, which promotes RhoA activity. Moreover, providing blood vessel- and radial glia-mimetic scaffolds for migrating neuroblasts promotes neuronal migration and improves functional gait behaviors after neonatal brain injury. In the V-SVZ, oligodendrocyte progenitor cells (OPCs) are also generated and migrate toward the surrounding white matter, where they differentiate and form myelin. After white matter injury in rodents, the production and subsequent migration of V-SVZ-derived OPCs are enhanced. In the neonatal period, administration of growth factors at a specific time promotes oligodendrocyte regeneration and functional recovery after brain injury. These findings suggest that activating the high regenerative capacity that is specific to the neonatal period could lead to the development of new therapeutic strategies for neonatal brain injury.

Keywords: biomaterials; brain injury; neural stem cell; neuron; subventricular zone.