Experimental Study Of The Neuroprotective Effects Of FK506 On Spinal Cord Injury In Dogs

Objective:Spinal cord injury occurs through various countries throughout the world with an annual incidence of 15 to 40 cases per million. No ideal medicine or method is available in spinal cord injury. FK506 is a macrolide antibiotic with major immunosuppressive properties , and is used in transplantation for the prevention of rejection . Several studies have reported a neuroprotective effect of FK506 in experimental models of cerebral ischemia or spinal cord injury . The present study is to explore the neuroprotective effects of FK506 on acute spimal cord injury in dogs and its mechanisms to searching for a new drug in the spinal cord injuty. Methods:Acute spinal cord injury was induced in anesthetized dogs with Allin's technique. Animals were randomly divided into three groups. Group A (n=8)was the control group and received operation but no therapy; group B(n=8), receiving a single dose of FK506(0.18mg/kg)was administered with a arterial duct at 2h after spinal cord injury(SCI); group C(n=8), receiving a single dose of FK506(0.3mg/kg)was administered with a arterial duct at 2h after SCI. MRI was performed at 30min,72h,1w after injury. Animals were evaluated neurologically 24h,48h,72h,1w,3w after injury . Neurological status was assessed by using the Xu shaoting scoring system. Dogs were randomly killed at 48h,1w,or 3w, and spinal cords were harvested for histopathology. Immunohistochemical technique and image analysis was used to examine the expression of NF200 in neurons and GFAP in astrocytes . Results:In all groups of animals showed less motion , malnutrition on earlier period(1-3 d). Neurological function scores showed gradual improvement over the 3w testing period , even in vehicle-treated controls . FK506(0.3mg/kg)treated dogs had significantly better neurologic outcome compared with control group at 48h,72h,1w,3w(P < 0.05?). FK506(0.3mg/kg )groups showed a better performance than FK506(0.18mg/kg )groups, but is not statistically significant . FK506 (0.18mg/kg )groups showed a better performance than control groups , but is not statistically significant . MRI:SCI mainly showed isointense on T1WI and hyperintense on T2WI .The signal scope of spinal cord injury on MRI was associated with the neurologic outcome .Histopathologic analysis disclosed the extent of local inflammatory cell infiltration in FK506 groups ( A and B ) was lighter than that in contral groups at 48h,1w,3w . The expression of GFAP and NF was significantly higher in group C than in group A at 1w,3w (P < 0.05 ) , The expression of GFAP and NF in group B was higher than in group A , but is not statistically significant . Conclusion:(1)Local administration of FK506 (0.3mg/kg) possesses neuroprotective function , which can improve neurologic recovery and attenuate second spinal cord injury .(2)Local administration of FK506 possesses a dosage-effect relation .