Effects of single or combined application of UDP-glucose, glial cell line derived neurotrophic factor and memantine on long-term prognosis of neonatal rats with periventricular leukomalacia

Abstract

Objective To explore the effects of the single or combined application of UDP-glucose,glial cell line derived neurotrophic factor (GDNF) and memantine on the long-term prognosis (physical development,learning and memory and limb function) of rats with periventricular leukomalacia (PVL).Methods Five-day-old SD rats were randomly divided into the sham-operated group,PVL group,PVL plus UDP-glucose group,and PVL plus UDP-glucose combining GDNF and memantine group (three drugs group).The rats in the sham-operated group were performed dissociation but not ligation of the right common carotid artery and given no hypoxia; those in the PVL group were given ligation and hypoxia; those in the PVL plus UDP-glucose group were given intraperitoneal injection of UDP-glucose after ligation and hypoxia and those in the three drugs group were given intracranial injection of GDNF and intraperitoneal injection of UDP-glucose and memantine after ligation and hypoxia.The rats were weighed before and immediately after the establishment of PVL models,and the day age of first time opening eyes was recorded.Both tests of Morris water maze and Rivlin inclined plane were performed in all rats of the 4 groups on 26 day age; the escape latency (EL),swimming distance and scores in different inclined angle were recorded and compared,respectively.Results The weight at each time interval reduced and the day age of first time opening eyes delayed significantly in the PVL group as compared with those in the sham-operated group,PVL plus UDP-glucose group and three drugs group (P＜0.05).The average EL and swimming distance in four quadrants in the PVL group were obviously longer than those in the other 3 groups (P＜0.05).The scores of inclined plane degrees at 45° and 50° decreased remarkably in the PVL group as compared with those in the other 3 groups (P＜0.05).No significant differences in the weight,day age of first time opening eyes,values of EL and swimming distance,and scores of inclined plane were observed either between PVL plus UDP-glucose group and three drugs group or between PVL plus UDP-glucose group/three drugs group and sham-operated group,respectively (P＞0.05).Conclusion The single or combined application of UDP-glucose,GDNF and memantine can improve significantly the long-term prognosis in rats with PVL; the combined use of UDP-glucose,GDNF and memantine tends to have much obvious improvement in these rats. Key words: Periventricular leukomalacia; UDP-glucose; Glial cell line derived neurotrophic factor; Memantine