Combination With Delayed Mild Hypothermia And Methylprednisolone After Ischemia/Reperfusion-induced Spinal Cord Injury In Rabbits

With a greater understanding of both primary and secondary mechanisms of spinal cord injury, the roles of calcium, free radicals, sodium, excitatory arm'no acids, and apoptosis have b een elucidated. But none of the approaches tried alone has been able to promote significant recovery. Combination strategy for spinal cord in ury may effectively enhance locomotor functional recovery.In recent years, growing evidence in animal and human studies has documented the beneficial outcome effects of mild hypothermia and Methylprednisolone (MP) to the spinal cord injury. Intraischemic and preischemic hyperthermia is known to aggravate neuronal damage. However, the effect of postischemic hyperthermia has not been addressed experimentally in much detail.The present study was designed to investigate whether combination therapy with mild hypothermia and MP could effectively enhance locomotor functional recovery on spinal cord ischemia-reperfusion (I/R) in rabbits. And to investigate the effect of mild hypothermia and combined with MP on the apoptosis of neurons and inflammation, which will be helpful to provide theory evidence for clinical treatment in the future.Design: In the current study,1 11 rabbits were randomly divided into five groups: group I (sham-operated, no I/R,n=7); group II (normothermia control group, only I/R, n=30), group III (I/R + hypothermia, rectal temperature38 ?0.5'C,beginning at 30min after I/R, n=30), group IV, (I/R + MP ,n=14), group V (I/R + MP + hypothermia, n=30). Spinal cord ischemia was induced by clamping the aorta below the left renal artery about 45min. Neurological outcome was assessed according to Jacob and Reuter's Score, then animals were sacrificed at 8h, 12h, 24h, 48h, 72h and 7d after reperfusion, and the spinal cord (L2-s) was removed for histopathologic examination (HE and TUNEL staining method), or measuring ths spinal LL-8 levels by ELASAmethod separately.Result: Mild hypothermia and Mild hypothermia +MP reduced histopathological changes, relative to normothermic controls. And neurological outcomes of Mild hypothermia, Mild hypothermia +MP group animals had significantly (P<0.01) less neurological deficits from postoperative 12 hour to 7 days compared with normothermic controls. The peak and the concentration of IL-8 in Mild hypothermia and Mild hypothermia +MP groups were significantly (P<0.05) less and slower than MP and normothermic control groups.Conclusion: Neuronal apoptosis and inflammation may be induced or aggravated in the process of spinal cord ischemia/reperfusion injury. Both postischemic hypothermia treatment alone and combined treatment of hypothermia with MP diminished neurona damage; the methods could effectively enhance locomotor functional recovery. Combination with hypothermia and MP could provide more protective effects on ischemia spinal cord than applying hypothermia or MP alone. An early and extended period of postischemic hypothermia provides a powerful and long-lasting protection in our study observation. The mechanism of protective effects may be related to reducing metabolic rate and apoptosis and inhibiting inflammation. Because of simple protocol e.nd good repetitive results, we thought the method could be used as a kind of ideal spinal cord ischemia hypothermia protective model, used for further study to inquiry into the hypothermia combining with other protective strategy.