The Effect Of Mycophenolate Mofetilglial On The Glial Scar Formation And The Learning And Memory Function In A Rat Model Of Diffuse Axonal Injury

ObjectiveTo investigate the intervention of mycophenolate mofetil(MMF) in the formationof glial scar and the learning and memory function in a rat model of diffuse axonalinjury.Methods1.A rat model of DAI established by an experimental device independently designed(Patent No.: ZL200920067463.4) for inducing simultaneous linear and angularaccelerations.2.The major constituents(microglia, astrosyte, chondroitin sulphate proteoglycan) ofglial scar are marked by using immunohistochemisty staining to investigate thechange with different time(1day,4days，7days,14days) between the rats ofsham-treated group and injured group.3.Glial scar of rats of the changes of the formation of are evaluated by usinghistopathology staining sham-treated group, Physiological Solution(NS)-treated groupand mycophenolate mofetil(MMF)-treated group is elavated to invetigate the changesof the formation by using techniques of immunohistochemisty staining, Morirs watermaze(MWM) and Image-Pro Plus(IPP)5.0sotfware at different time(7days,14days，28days). And to elavate the intervention of mycophenolate mofetil(MMF) in theformation of glial scarand the learning and memory function in a rat model of diffuseaxonal injury.Results1. Transmission electron microscopy showed a series of ultrastructural ARB, demyelination, vacuolization of myelin sheaths or disintegration of myelin sheaths.Immunohistochemical staining showed the formation of glial scar in vulnerable areasof injury group.2.Compared with the sham-treated group, the number of microglia, astrosyte andintegrated optical density(IOD) values of chondroitin sulphate proteoglycan invulnerable areas in injury group creased significantly; The number of microgliastarted to increase at1day post-trauma, peak at4days post-trauma, and then decreasegradually with time, but still more than the normal group; Astrocyte was littleactivated1day post-trauma, then increase gradually with time, and go to balance at14days post-trauma; Chondroitin sulphate proteoglycan was tested by4dayspost-trauma, then correlated positively with the number of astrocyte.3.Compared with the sham-treated group and Sodium Chloride PhysiologicalSolution(NS)-treated group, the number of microglia, astrosyte and integrated opticaldensity(IOD) values were significantly decreased in vulnerable areas ofmycophenolate mofetil(MMF)-treated group at different time(7days,14days,28days);At7days post-trauma, the number of microglia, astrosyte and integrated opticaldensity(IOD) values of chondroitin sulphate proteoglycan show no correlation withthe mean parameters of MWM; but a significant correlation at28days post-trauma.Conclusions1.DAI rats showed the pathological changes of widespread ARBs, vacuolization ofmyelin sheaths or disintegration of myelin sheaths. Immunohistochemical stainingshowed the formation of glial scar in vulnerable areas of injury group around oramong the site of injury axons, also it changes regularly with time.2.Mycophenolate mofetil(MMF) shows a significant depressant effect on theformation of glial scar atfer DAL At the acute stage, Mycophenolate mofetil(MMF)shows no significant effect on the studying and memory function, but a significantpromotion during the long-time recovery.3.In the acute stage of DAI, The mount of glial scar in vulnerable areas show nocorrelation with the mean parameters of MWM; But in recovery stage, the mount of glial scar in vulnerable areas show a significant negative correlation with the meanparameters of MWM.