Chronic anterior thalamic nucleus deep brain stimulation reduces gliosis and neuronal loss in hippocampal CA2 and CA3 regions of epileptic rhesus monkeys

Background and objective: Anterior thalamic nucleus deep brain stimulation (ATN-DBS) has been shown to be an effective method in seizure reduction. However, its underlying mechanisms remain unclear. This study aimed to determine the potential beneficial effects of ATN-DBS on hippocampus in epileptic rhesus monkeys. Methods: Eighteen rhesus monkeys were randomly divided into three groups: control group (n=6), sham-DBS group (n=6) and DBS group (n=6). ATN-DBS was applied to kainic acid (KA)-induced epileptic monkeys. Behavioral seizures were continuously recorded. Neuronal nuclei (NeuN), hematoxylin and eosin (H&E) and glial fibrillary acidic protein (GFAP) staining were used to assess hippocampal injury and the effects of chronic ATN-DBS. NeuN and caspase-3 levels were evaluated by western blot. Results: Seizure frequency was 45.1% lower in the DBS group compared with the sham-DBS group (P<0.05). In the DBS group, H&E and NeuN staining revealed more cells in the CA3 region (P<0.05), while GFAP staining showed less GFAP-positive cells in both CA2 (P<0.01) and CA3 (P<0.05) regions, compared with the sham-DBS group. Furthermore, caspase-3 levels decreased (P<0.05, vs. the sham-DBS group) and NeuN levels increased (P<0.05, vs. the sham-DBS group) in the DBS group. Conclusion: These results suggest that ATN-DBS can reduce gliosis and neuronal loss in hippocampal CA2 and CA3 regions in epileptic rhesus monkeys, which may be one of the most important mechanisms in treating epilepsy with ATN-DBS.