Ranolazine attenuates brain inflammation in a rat model of type 2 diabetes

Abstract Recent studies suggest a pathogenetic association between metabolic disturbances, including type 2 diabetes (T2DM), and cognitive decline and indicate that T2DM may represent a risk factor for Alzheimer disease (AD). There are several experimental evidence that ranolazine, an antianginal drug, may act as a neuroprotective drug. The aim of the present study was to evaluate the effects of ranolazine on hippocampal neurodegeneration and astrocytes activation, in a T2DM rat model. Diabetes was induced by high fat diet (HFD) and streptozotocin (STZ) injection. Metformin, a widely employed hypoglycemic drug, has been used as positive control. Animals were divided into the following groups: HFD/STZ + Ranolazine, HFD/STZ + Metformin, HFD/STZ + Vehicle, NCD + Vehicle, NCD + Ranolazine, and NCD + Metformin. The presence of neurodegeneration was evaluated, in hippocampal cornus ammonis 1 (CA1) region, by cresyl violet staining histological methods, while astrocytes activation was assessed by Western blot analysis. Staining with cresyl violet highlighted a decrease in neuronal density and cell volume in the hippocampal CA1 area in of the diabetic HFD/STZ + Vehicle rats Ranolazine and Metformin both improved T2DM-induced neuronal loss and neuronal damage. Moreover, there was an increased expression of GFAP in HFD/STZ + Vehicle group, compared to either NCD and HFD/STZ animals receiving ranolazine or metformin. In conclusion, in the present study, we provided insights on the mechanisms through which ranolazine may counteract cognitive decline in diabetic patients.