141. Autophagy induction contributes to the neuroprotective effect of intermittent fasting in experimental spinal cord injury

Abstract

BACKGROUND CONTEXT Spinal cord injury (SCI) is one of the leading causes of neurological disability and death. So far, there is no satisfactory treatment for spinal cord injury due to its complex and ill-defined pathophysiology. Recently, autophagy has been implicated to be protective in acute spinal cord injury rat models. PURPOSE We aimed to investigate the therapeutic value of a dietary intervention, namely, intermittent fasting (IF), on neuronal survival after acute SCI and its underlying mechanism relating to autophagy regulation. STUDY DESIGN/SETTING Experimental spinal cord injury in rats. PATIENT SAMPLE One hundred rats. OUTCOME MEASURES Behavioral test, Western blot, immunofluorescence and TUNEL staining were applied in the current study. METHODS Male Sprague–Dawley rats were randomly divided into the following groups: ad libitum feeding (ALF) group, ALF+acute SCI group, IF group, IF+acute SCI group and ALF+ acute SCI+3-methyladenine (3-MA) group. RESULTS We found remarkable improvement in the behavioral test in the IF group. Western blot revealed marked decrease of cleaved caspase-3 level as well as bax/bcl-2 ratio in the IF group, suggesting an inhibition of intrinsic apoptosis pathway. immunofluorescence further revealed more NeuN-positive cells in the IF group, revealing that IF preserved more neurons after acute SCI. In addition, the expression of autophagy markers like LC3-II and beclin 1 were also increased in the IF group compared to the ad libitum feeding group that underwent acute SCI, while p62, the substrate protein of autophagy, presented considerable decrease, suggesting an up regulation of autophagy by IF. Blocking autophagy with 3-MA, a selective inhibitor of autophagy, reversed the down regulated apoptosis-related markers by IF, further validating that the neuroprotective effect of IF was associated with autophagy enhancement. CONCLUSIONS Taken together, the above findings suggest that IF exerts a neuroprotective effect in acute SCI via up regulating autophagy and dietary interventions could be promising for SCI treatment. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.