| Previous researchs suggested that the Ketogenic diet(KD)is neuroprotective to many neurodegenerative diseases.Our pilot study indicated that KD and Every-other-day-ketogenic diet(EODKD)upregulateed histone acetylation and played a role of anti-oxidative stress in tissue of acute spinal cord injury(SCI).This study base on the establishment of a cervical spinal cord hemicontusion injury model with displacement control,and discusses that the effect of ketone body metabolisms on inhibiting oxidative stress in SCI and the characterization of behavioral and histological in secondary SCI.Part ? Model of cervical spinal cord hemicontusion injury with displacement controlBackground and objective:A hemicontusion cervical SCI rat model has been developed with force control.The present study aims to develop a hemicontusion cervical SCI model under displacement control.Methods:The hemicontusion cervical SCI was performed on 15 adult male SD rats.A 1.5-mm-in-diameter impactor 22.5° laterally and 1.4 mm off-set was driven to compress the unilateral C5 cord 2.2 mm at 600 mm/s.The electrophysiological assessment and forelimb functional assessments were performed before and after injury.Histologic analysis was performed in 4w post-injuryResults:The actual contusive displacement and speed were accurate.The average contusive compressive force was 1.514±0.369N.The most severe tissue damage was at the epicenter,with loss of the ventral horns of gray matter and lateral funiculus of white matter.Both ipsilateral and contralateral forelimb MEP showed latency prolongation and amplitude reduction after injury.The MEP amplitude increased with time after injury,with the ipsilateral persistently lower compared to the contralateral.The ipsilateral MEP latency decreased over all the time after injury,with significant difference between sides.There was no difference in the SEP latency among time points and between sides.An obvious damage of the ipsilateral motor function in behavioral assessment after injuryConclusion:Our cervical spinal cord hemicontusion models with displacement control have consistent and accurate biomechanical parameters to the spinal cord at a higher speed,while shows a typical unilateral impairment in behavior,electrophysiology and histology.Part ? Effect of ketone body metabolism on anti-oxidative stress in rats after SCIBackground and objective:Our previously study have demonstrate that ?OHB improves the capability of ant-oxidative stress in acute SCI.The objective of the present study was to further investigate the effect of KD on promoting the histone acetylation and improving the capability of ant-oxidative stress in secondary SCIMethods:39 male SD rats were randomly divided into 3 group fed with KD,standard diet(SD)and Sham group up to 2 weeks.Rats were strict to its diet after hemicontusion.Levels of blood ketones and blood glucose were measured for each group.Samples of spinal cord tissues were harvested at different time points after injury,western bolt to detect the expression of the HDAC's subtypes,the histone acetylation protein,NAD(P)H oxidase,protein carbonylation and the anti-oxidative stress protein,and tissue homogenates for lipid peroxidation.Results:Level of ketone body was dramatically increased in KD group.Expression of HDACs Subtype from the KD groups was significantly inhibited,while the expression of histone acetylation significantly increasing.The level of MDA and DNP in KD group was significantly lower than the level in the SD group.The content of Mn-SOD,catalase and Foxo3a in KD group was higher than that in SD group after injury,and there was a significant difference between two groups.Conclusion:The present results indicated that a pre-exist high level of ketone body could inhibition of HDAC activity,increasing histone acetylation in spinal cord and upregulate anti-oxidative stress in the spinal cord after secondary injury.Part ? Neuroprotective effect of ketone body metabolism in secondary cervical SCI.Background and objective:KD and EODKD promote neuroprotection.EODKD increase level of ketone body.Here,we investigated the efficacy of KD and EODKD as a treatment for cervical SCI in rats.Methods:40 male SD rats following C5 hemicontusion injury,were fed either SD,KD or EODKD.The forelimb functional recovery was evaluated for 12 weeks,followed by quantitative histopathology.Results:Without causing weight loss,post-injury KD and EODKD treatment resulted in remarkably increased level of blood ketone body.Furthermore,KD and EODKD fail to significantly improve behavioral recovery of ipsilateral forelimb function.Histologically,the spinal cords of KD and EODKD treated animals displayed smaller lesion areas at the edge of epicenter,while no beneficial effect on white matter and gray matter sparing.Conclusion:Post-injury ketone body metabolism did not significantly promote functional recovery after cervical SCI,but decrease lesion area.Maybe this difference to results of the previous study dues to the hemicontusion model we chose. |
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