Objective: Perinatal White Matter Injury (PWMI) is the leading cause of cerebral palsy and other neuorocognitive deficits in prematurely born children. There is currently no restorative therapy available in PWMI, but cell therapy has been widely discussed.  The objective of this study was to determine the fate and effect of glial restricted precursor cell (GRP) transplantation in an ischemic mouse model of PWMI.

Methods: Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P22, intracallosal injections of either eGFP-GRP cells or normal saline were performed in control and ligated mice. Neurobehavioral, and postmortem studies were performed at various time points between 1, 4 or 8 weeks post-transplantation.

Results: GRP survival was comparable at 1 month but significantly lower at 2 month post-transplantation in PWMI mice compared to control. Surviving cells showed better migration capability in controls, however, the differentiation capacity of transplanted cells was similar in control and PWMI mice. There was a significant increase in mean hemispheric myelin basic protein density along with a significant decrease in SMI32 staining in GRP-transplanted PWMI mice compared to saline-treated PWMI mice. Saline-treated PWMI mice showed a significant reduction of startle amplitude compared to controls, while this abnormal behavioral response was completely abolished in GRP-transplanted animals.

Interpretation: Despite reduced survival of transplanted GRP cells, these cells improved behavioral and neuropathological outcomes in an ischemia-induced PWMI model. Further research is needed to determine the mechanisms by which these precursor cells lead to amelioration of PWMI.