Abstract Sa1108: The Aberrant Autophagy-Apoptosis regulation Mediates the Severe Neurological Dysfunction after Cardiac Arrest in Diabetic Mice

Background: Patients with diabetes have lower survival and worse neurological outcome after cardiopulmonary resuscitation (CPR) compared with non-diabetes. Previous studies have mentioned the aberrant autophagy in diabetic mice. However, whether this abnormal autophagy exacerbates neuronal apoptosis and neurological outcome in diabetic mice remains unclear. Methods: Patients were divided into non-diabetic cardiac arrest (CA) patients and diabetic CA patients, and the survival and neurological outcomes at discharge and day 28 after ROSC were compared between these two groups. Diabetic mice were fed with high fat diet (HFD), and CA model was established by inducing ventricular fibrillation electrically. The neurological prognosis was assessed by open field test (OPT), novel object recognition (NOR) and Y-maze. Neuronal apoptosis and autophagy were evaluated by immunofluorescence and western blotting, including TUNEL, cleaved caspase 3, LC3B, p62 and beclin1. Results: Compared with non-diabetic patients, the survival at discharge and at day 28 after ROSC are significantly lower in IHCA patients with diabetes. Meanwhile, the neurological deficits at discharge and at day 28 after ROSC are much severer in diabetic-CA patients. In addition, the lower survival and worse neurological function have been discovered, and the cognition impairment is more significant after ROSC in HFD mice. Neuronal apoptosis is severer in HFD mice. In ND mice, the activated autophagy has been revealed after CA-CPR-ROSC, however, autophagy can not be activated after ROSC in HFD mice since the baseline autophagy is at a higher level when compared with ND mice. Neuronal apoptosis is exacerbated after autophagy inhibition by 3-MA in ND mice, while after autophagy activation by rapamycin in HFD mice, apoptosis is attenuated after ROSC. Conclusion: Diabetes is the risk factor for neurological outcome in IHCA patients. The aberrant autophagy regulation in cortex neurons contributes to the severe apoptosis and neurological deficits after ROSC in diabetic mice.