Effect Of Rehabilitation Training Combined With Methylprednisolone On Neurological Function After Spinal Cord Contusion In Rats

Objective:This study examined the effect of rehabilitation training combined with methylprednisolone(methylpredisolone,MP)on the recovery of histomorphology and motor function after spinal cord contusion in rats.To observe the effect of inhibiting the formation of glial scar and promoting nerve regeneration,and compare the effect of drug therapy combined combined with exercise rehabilitation training on neurological function of spinal cord injury.To explore the mechanism of recovery of nerve function on exercise training after spinal cord injury and provide experimental basis for further suitable and effective clinical rehabilitation strategies.Methods:Adult SD rats were randomly divided into Sham group,Model group,MPgroup,and Exercise training combined methylpredisolone(MP+Ex)group.Rat spinal contusion cord model was prepared by Pinpoint Precision Cortical Impactor? apparatus and at posttraumatic 30 min methylprednisolone(30mg·kg-1·BW)was administrated through tail intravenous infusion.From one week after surgery animal was received treadmill exercise program and maintained six weeks regularly.Harris HE staining method combined with Luxol Fast Blue(LFB)staining was employed to inspect the morphological changes of damage tissues.PCR and immunohistochemical staining techniques were used to estimate Nogo receptor(Ng R)and chondroitin sulfate proteoglycans(CSPGs)m RNA levels,respectively.All adult SD rats were trained for six days on on the animal experiment treadmill,and then randomly divided into for groups: Sham group,Model group,MP group,MP+Ex group.Rat spinal contusion cord model was prepared and at posttraumatic 30 min methylprednisolone(30mg·kg-1·BW)was administrated through tail intravenous infusion.Tread Scan gait analysis system was used to describe the gait behavioral characteristics at 1,2,4,6 week.PCR and Western-blot techniques were used to detect the expression of PCR m RNA and protein of brain derived neurotrophic factor(BDNF)at 1,3,5 week after spinal cord contusion in rats.At 6 week of posttraumatic,Neu N staining and TUNEL staining was used to detect the survival rate of neurons and neuronal apoptosis in the injured area respectively;the positive expression of glial fibrillary acidic protein in astrocytes at the injured site were observed and the level of GFAP m RNA was detected.Results:Rehabilitation training combined with methylprednisolone therapy can significantly reduce the degree of tissue degeneration and increase residual myelin sheath area(P < 0.05),The area of positive Ng R and CSPGs and the relative expression of m RNA significantly decreased(P <0.05).Compared with drug treatment alone,rehabilitation training combined with methylprednisolone therapy can significantly improve the stride time,print area,stride length,swing time,regularity index,minimum longitudinal deviation(P<0.05).At the same time,the number of necrotic neurons,the inhibition rate of astrocytes and scar in the anterior horn of gray matter and 3mm and 5mm were significantly lower than those in group MP(P<0.05).Compared with Model group,the BDNF m RNA and protein levels in MP group were only significantly higher than those at 1 week(P<0.05).In contrast,the expression of BDNF m RNA and protein in MP+Ex group were significant increased at 1,2,3,5 week after injury(P<0.05),and at 2,3 week BDNF m RNA and protein levels were significantly higher than those in Model group(P<0.01).The protective effect of MP +Ex group was significant(P<0.05),and the number of MP + Ex group was significantly higher than that of MP group(P<0.05)at the center of injury center ±3mmand ±5mm.There was a large number of TUNEL positive cells in the gray matter of the Model group,and exercise training combined with methylprednisolone treatment could significantly inhibit the expression of TUNEL positive cells(P<0.05).Rehabilitation training combined with MP treatment can inhibit the activation of astrocytes by reducing the expression of GFAPm RNA and protein content(P<0.05).After the drug treatment of one week appropriate intervention rehabilitation training for the treatment of SCI play a beneficial effect,and with the extension of time,the effect is more prominent,2,3 week treatment effect is the best.Conclusion:Rehabilitation training combined with methylprednisolone therapy can effectively promote the recovery and reconstruction of nerve function after SCI in rats,and the effect is better than single MP impact therapy.This combination therapy is suitable for long-term use,the main mechanism probably is reducing myelin loss,inhibiting the formation of glial scar,and increasing the expression of BDNF,reducing neuronal apoptosis,improvementing microenvironment of nerve regeneration and motor function,and thus promoting the repair and regeneration of the injured spinal cord.