Changes Of LINGO-1 Expression At The Edge Of Lateral Ventricles Of Rats With Experimental Autoimmune Encephalomyelitis

ObjectiveOur experiment is designed to observe the time interval changes of the expression of LINGO-1 at the edge of lateral ventricles of rats with experimental autoimmune encephalomyelitis(EAE),and to explore the possible function of LINGO-1 in the happening and development of EAE, and meanwhile it is expected to provide available clues or experimemtal evidences about treating EAE by LINGO-1 antagonist methods in certain time interval.MethodsThe animal model was established in female Wistar rats by immunizing rats with guinea pig spinal cord homogenate(GPSCH),complete freund's adjuvant(CFA) and pertussis vaccine(PV).Fifty wistar rats were randomly divided into two groups:twenty-five rats in EAE group and twenty-five in control group(the rats in control group were injected with sodium chloride and CFA),then the two groups were randomly divided into five subgroups, each subgroup had five rats,the rats of five subgroups in both groups were respectively sacrificed on the 11th day,the 15th day,the 18th day,the 24th day and the 30th day.The severity of EAE was scored on a scale 0～5 according to the signs and symptoms.Histological examinations were performed on the sections of brain with the aid of hematoxylin-eosin and Luxol fast blue-Cresyl fast violet myelin staining.The number of inflammation focus in the central nervous system(CNS) was counted under the optical microscope.And the expression of LINGO-1 in brain tissue was detected by using immunohistochemistry technique.Experimental results were analyzed with SPSS 16.0.Results1.The morbility of the control group was 0%,the scores were 0 and no weight loss.The morbility of EAE group was 88.00%;The clinical symptoms of EAE occurred about 9 days after immunization,the peak of clinical symptoms took place on the 14th or 15th day,then the symptoms were gradually relieved;The scores were growing with the disease deterioration,and decreasing with disease relief,the scores were up to the peak on the 15th day;the weight loss of EAE group was the most obvious on the 15th day.2.The CNS tissue's hematoxylin-eosin(H-E) staining histopathology results of EAE group's rats indicated that CNS already had inflammation focuses on the 11th day,the extent and amount of the inflammation focuses were increased on the 15th day,then decreased on the 18th and 24th day, reached the normal level on the 30th day.Compare the number of inflammation focus among the five subgroups of EAE:the 15th day subgroup's were maximum;respectively comparing the 15th day's and the 11th day's,the 15th day's and the 24th day's had obvious differences(P＜0.01)3.Luxol fast blue-Cresyl fast violet myelin staining indicated:no demyelination in control group.In EAE group,the 11th day later the demyelination lesions could be seen;on the 15th day the demyelination lesions were the most serious,large piece and fused demyelination focuses could be seen,even neuraxis were absent,and vacuoles were seen;on the I8th day and the 24th day demyelination was reduced;on the 30th day dispersive demyelination focuses could be seen casually.4.Immunohistochemistry analysis results of each group rats indicated: Comparing to the five subgroups of control group:the expressions of LINGO-1 at the edge of lateral ventricles tissue had no differences(p＞0.05).Comparing the same period subgroups of EAE and control group:the expressions of LINGO-1 of the 11 th day(P＜0.05) and the 15 th day(P＜0.01) of EAE group were decreased;the expressions of LINGO-1 of the 18th day of EAE were slightly increased,but(p＞0.05);the expressions of LINGO-1 were obviously increased on the 24th day and the 30th day(P＜0.01).Comparing to the LINGO-1 expressions among the five subgroups of EAE:with the disease lasting,the LINGO-1 expressions of the 15th day were obviously decreased comparing to those of the 11th day(P＜0.01);then the LINGO-1 expressions of the 18th day were increased comparing to those of the 15th day(P＜0.01);the LINGO-1 expressions of the 24th day were continuously increased comparing to those of the 18th day(P＜0.01);and the LINGO-1 expressions of the 30th day were decreased comparing to those of the 24th day(P＜0.01).ConelusionThe expressions of LINGO-1 have a dynamic change at the edge of lateral ventricles of EAE rats.LINGO-1 plays a significant inhibitory role in the development of EAE,especially in aspects of repairment and structure remodeling of impaired nerves and myelin during the recovery period of EAE.