Periventricular leukomalacia long-term prognosis may be improved by treatment with UDP-glucose, GDNF, and memantine in neonatal rats.

Abstract The therapeutic effects of UDP-glucose (UDPG), an endogenous agonist of GPR17 that may promote the self-repair of white matter, glial cell line-derived neurotrophic factor (GDNF), a neurotrophic factor correlated with the growth and survival of nerve cells, and memantine, an antagonist of NMDA receptors, were evaluated for functional improvement of neonatal rats with experimental periventricular leukomalacia (PVL). Five day-old neonatal rat pups were subjected to an ischemia-induced model of PVL. The pups were then randomly divided into sham, PVL, PVL plus UDPG, PVL plus GDNF, and PVL plus memantine groups. All pups were weighed and the age at first eye opening recorded. Pathological changes and myelin sheath formation in the white matter were assessed under both light and electron microscopy on day 7 and 21 after induction of PVL. Values of escape latency (EL) and swimming distance (SD) in Morris water maze test, and the modified inclined plane scores in Rivlin inclined plane test were recorded for rats on day 26. Pups in the PVL group were found to be significantly lower in weight ( p p p p p p