The Effect Of Epothilone B On Glial Cells In The Spinal Cord

Objective:The CCSCI(chronic compression spinal cord injury)models were established by placing a polyurethane film which could gradually expand under the C5 lamina.To investigate the effect of epo B(epothilone B)on the pathological changes of spinal cord tissue,astrocyte hyperplasia,glial scar formation and neurological function recovery after CCSCI,and to explore its possible mechanism.Method:Sixty-four male SD rats were randomly divided into group A,B,C.Group A was blank control group(n = 16),and C6 laminates were removed only.Group B was CCSCI group(24 rats),after exposuring and removaling of C6 laminectomy,the polyurethane film was placed on the epidural surface of C5,and the spinal cord was compressed by the expansion film slowly.The CCSCI models were established after 7 days.Group C was CCSCI with epo B treatment group(24 rats),CCSCI models were established as group B,epo B was injected intraperitoneally on the 7th and 14 th day.Rats in group B were intraperitoneally injected with the same amount of epo B solvent.The BBB score of each rat was recorded,before surgery and the 7th,14 th,21th,28 th day after the surgery,to determine the effect of epo B on motor function.The HE staining,TUNEL staining,IHC(immunohistochemistry),and WB(westernblot)test were implemented.Result:There were no significant differences in BBB scores between the groups(P> 0.05)before the operation.On the 7th day after operation,the BBB scores of group B and C met characteristics of CCSCI.HE staining found: tissue in group A was distribution,gray matter and white matter structure was clear,the central tube was round,in group B and C,white matter collapse,interstitial capillary compression deformation,neuronal and glial cell edema could be observed in the compression side of the spinal cord.TUNEL staining found: a small number of positive cells were found in group A,and the positive cells in group B and C were significantly increased(P <0.05).IHC and WB showed that the expression of GFAP in group B and C was higher than that in group A(P <0.05).At this time,the motor function and pathology of groups B and C meet CCSCI characteristics.On 14 th days after surgery,the BBB scores of B and C group were improved compared to 7 days' after surgery,and group C was significantly higher than the B group(P <0.05).Compared the HE staining in group B and C,obvious tissue liquefaction,neuronal nuclear pyknosis with a decrease in the number of visible vacuolization,axonal myelination damage significantly were found.C group was in the weaving degree of light,and less neuron lost.TUNEL(+)cells were significantly higher in the group B and C than those before,which had reached the maximum value,however,the number of TUNEL(+)cells in group C was significantly lower than that in group B(P <0.05).The expression of GFAP in group B and C was increased in IHC and WB,but group B was significantly higher than C group(P <0.05).After 21 days,the BBB score of group C was significantly better than that of group B(P <0.05).HE staining showed that in the group B,the network structure was formed,the neurons were significantly reduced,the oligodendrocytes proliferated and surrounded the axons and the scar tissue was formed.In the C group,the number of gray matter neurons decreased with a small amount of scar tissue formation.TUNNEL(+)cells in group B and group C were lower than before,and the decrease of group C was more than that of group B(P <0.05).The results of IHC and WB in group B and group C showed that the amount of GFAP increased compared with that before,and group B was significantly higher than group C(P <0.05).On the 28 th day,there were no significant changes.Conclusion:Rats with the CCSCI,could improve the spinal cord tissue edema,reduce spinal cord neurons and glial cell apoptosis,inhibit glial cell proliferation,reduce the compression of spinal cord neonatal scar formation,promote Neuronal axon repair,and thus promote the recovery of neurological function by intraperitoneal injection of low doses of epo B.The therapeutic effect is due to intraperitoneal injection of epo B,which can quickly through the blood-brain barrier,and enriched in the central nervous system.Epo B could be associated with microtubules associated with tau protein to regulate microtubule kinetics,inhibit the migration of scar fibroblasts,It also increase in microtubule bundles that promote the repair of axons.