Transplanted glial restricted precursor cells improve neurobehavioral and neuropathological outcomes in a mouse model of neonatal white matter injury despite limited cell survival

摘要: Objective Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy and other neurocognitive deficits in prematurely-born children, no restorative therapies exist. Our objective was to determine fate effect glial restricted precursor cell (GRP) transplantation an ischemic mouse model NWMI. Methods Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal-Day 5 (P5). At P22, intracallosal injections either enhanced green fluorescent protein (eGFP) + GRPs or saline were performed control ligated mice. Neurobehavioral postmortem studies at 4 8 weeks post-transplantation. Results GRP survival comparable 1 month but significantly lower 2 months post-transplantation NWMI compared with unligated controls. Surviving cells showed better migration capability controls; however, differentiation capacity transplanted similar NWMI. Saline-treated altered response startle amplitude prepulse inhibition (PPI) paradigms controls, while these behavioral tests completely normal GRP-transplanted animals. Similarly, there significant increase hemispheric myelin basic density, along decrease pathologic axonal staining cell-treated saline-treated animals. Interpretation The reduced long-term ischemia-induced suggests that neonatal ischemia leads long-lasting detrimental effects oligodendroglia even after initial insult. Despite limited GRP-survival, behavioral, neuropathological outcomes improved GRP-transplantation. results suggest exogenous improve myelination through trophic addition into mature oligodendrocytes. GLIA 2015;63:452–465