Aspirin Promotes The Differentiation Of Neural Stem Cells Into Oligodendrocytes And Enhances Their Maturation

Brain white matter lesion (WML) induced by chronic cerebral ischemia is sopopular in the aged. Its main pathological changes are axon degeneration anddemyelination after oligodendrocytes impairment. Though many patients sufferfromreduction of cognitive function, no effective therapy is available now. It hasbeen reported that neural stem cells (NSC) and other cells in brain of matureanimals can differentiated to oligodendrocyte precursor cells (OPC) under someconditions and OPC can supply lesion sites with new oligodendrocytes. So,screening for drugs which can promote the differentiation of OPC or OLs is apromising strategy to repair white matter lesion. In our former work, we find thatAspirin, a widely prescribed NSAIDs, can effectively promote the differentiationof NSC to OPC in vivo. We conducted this experiments in order to furtherinvestigate whether the aspirin can promote the differentiation of neural stem cells into oligodendrocytes and enhance them maturation in the brain ofmammals, and provided new evidences that aspirin may be used to repair WML.In this study, using rat chronic cerebral ischaemia model induced by2-VO,the number of new OLs and OPC were counted after30days. By this way, wecan find out the effect of aspirin promoting the OPC maturity and differentiationin the brain of mammals. And thus provide experimental evidences for a new useof aspirin. The results were as follow:(1)The number of newly-differentiated OPCs singnificantly decreased at SVZin model group compared with sham surgery group and normal group（P<0.05）.There were no statistical difference between sham surgery group and normalgroup.(2)The number of newly-differentiated OLs singnificantly decreased at CC inmodel group compared with sham surgery group and normal group（P<0.05）.There were no statistical difference between sham surgery group and normalgroup.(3)The immunofluorescent intensity of CNPase singnificantly decreased atCC in model group compared with sham surgery group and normal group（P<0.05）. There were no statistical difference between sham surgery group andnormal group.(4) Aspirin can increase the number of newly-differentiated OPCs at SVZ.The number of newly-differentiated OPCs singnificantly decreased at SVZ incontrol group compared with aspirin groups and normal group（P<0.05）; Therewere no statistical difference between aspirin group1(25mg/kg/d, ASA i.p.) andnormal group, but have statistical difference in other treatment groups.Thenumber of newly differentiated OPCs at SVZ of aspirin group3(100mg/kg/d,ASA i.p.) were higher than aspirin group1(25mg/kg/d, ASA i.p.) and aspiringroup2(50mg/kg/d, ASA i.p.)（P<0.05）. The number of newly differentiatedOPCs at SVZ of aspirin group4(200mg/kg/d, ASA i.p.) were higher than aspirin group1(25mg/kg/d, ASA i.p.（)P<0.05）.. There were no statistical difference inthe other treatment groups.(5) Aspirin can increase the number of newly-differentiated mature OLs atCC compared with control group（P<0.05）. The number of newly differentiatedmature OLs at CC of aspirin group4(200mg/kg/d, ASAi.p.) were significantlyreduced compared with aspirin group1(25mg/kg/d, ASAi.p.), aspirin group2(50mg/kg/d, ASAi.p.), aspirin group3(100mg/kg/d, ASAi.p.)（P<0.05）. But,there were not statistical difference between aspirin group4(200mg/kg/d ASAi.p.)and normal group; There were no statistical difference every two groups ofaspirin group1(25mg/kg/d, ASAi.p.), aspirin group2(50mg/kg/d, ASAi.p.) andaspirin group3(100mg/kg/d, ASAi.p.).(6) The quantity of PDGFaR in CC was detected by WB. Treatment withaspirin were significantly reduced compared with normal group, control groupand sham surgery groups; Aspirin group2(50mg/kg/d, ASA i.p.) and aspiringroup3(100mg/kg/d, ASA i.p.) and aspirin group4(200mg/kg/d, ASA i.p.) weresignificantly reduced compared with aspirin group1(25mg/kg/d, ASA i.p.). Therewere no statistical difference every two groups of normal group、control groupand sham surgery groups.In conclusion, low-dose aspirin treatment after2-VO increased the number ofrenascent mature OLs and OPCs, which maybe owe to low-dose Aspirin canpromote NSCs differentiate into OLs and OPCs,and induce OPC transformationmature OLs.So,it can recovery the white matter lesion.