Histological assessment of the hippocampus in type 2 diabetic rats: Neuroprotective roles of exenatide, empagliflozin, and quercetin

This study aimed to evaluate the histological changes in hippocampal tissue following exenatide, empagliflozin, and quercetin monotherapy, as well as combined treatment, in rats with type 2 diabetes. The rats were divided into 7 groups: group 1 (non– diabetic control), group 2 (diabetic control), group 3 (diabetic + sham), group 4 (diabetic + exenatide, 10 μg·kg⁻¹), group 5 (diabetic + empagliflozin, 50 mg·kg⁻¹), group 6 (diabetic + quercetin, 50 mg·kg⁻¹), and group 7 (diabetic + combination treatment). The study lasted for 8 weeks. At the end of the study, brain tissues of the rats were collected and fixed in 10% buffered formaldehyde. After fixation, routine tissue processing was performed, and paraffin blocks were created. May–Grünwald Giemsa staining and Argyrophilic nucleolar organizer region staining were applied to the paraffin sections. The CA1, CA3, and dentate gyrus regions of the hippocampus were evaluated. The study revealed an increase in the number of shrunken, dark neurons with pyknotic nuclei in diabetic rats, while a decrease in the number of healthy neurons was observed. Cell proliferation was assessed using Argyrophilic nucleolar organizer region staining, which showed that diabetes causes a decrease in cell proliferation. Exenatide, empagliflozin, and quercetin ameliorated the diabetes–induced decrease in the number of healthy neurons, and combination therapy yielded better results than monotherapy.