The Effect on Differentiation and Maturation of Oligodendrocyte by Age of Cerebral Palsy Modeling Using Sprague Dawley Rat

Abstract

Cerebral palsy induces motor, cognitive, attention, and behavioral dysfunctions caused by brain damages. It is caused by damage to oligodendrocyte induced hypoxic ischemia and injection in the perinatal period. Therefore, an animal models that performed hypoxiaischemia-lipopolysaccharide injection (HIL) at 4-7 days of age (PND) are widely used. However, there is a difference in the brain damage due to exposure time under the hypoxic condition, gender, and ligation surgery techniques. In this paper, the optimal surgical age was found by analyzing behavioral tests, inflammatory reactions, and the differentiation and maturation of oligodendrocytes by performing HIL on rats 4, 5, 6, and 7 days old, respectively. On the 4th, 5th, 6th, and 7th days of birth (PND) of male Sprague Dawley rats, the right common carotid artery was ligated, they were incubated in an environment of 37℃, 92% N2, and 8% O2, and then peritoneally injected LPS (1 mg/kg) after removing the ligation. The rota-rod test were performed at PND 10, 20, 30, and 40, and memory tests such as passive avoidance and Morris water maze tests were performed on PND36-40, and then they were euthanized to analyze inflammatory indicators (NF-kB, TNF-a, IL-6, iNOS, and COX2) and indicators of the differentiation and maturation (Olig2, CNPase). In the case of the PND4 group, the limb coordination test were significantly different from that of the normal group, but there was no difference in other analyses. In the case of PND5 group, there were significantly differences in limb coordination tests, memory tests, inflammatory indicators, and differentiation and maturation of oligodendrocyte. In the case of the PND6 group, there was a significantly difference in limb coordination and memory tests, and a significantly increase in inflammatory indicators compared to other groups, but the mortality rate increased and indicators of the differentiation and maturation of oligodendrocyte were increased. In the case of the PND7 group, the limb coordination test showed significantly differences compared to normal group, but there was no difference from the normal group in other analyses. In conclusion, this study suggests that the PND5 group, where abnormal behavioral tests, an increase in appropriate inflammatory indicators, and a decrease in maturation and differentiation-related proteins of oligodendrocyte are comprehensively observed, is most suitable.