Role Of Anterior Thalamic Nucleus In Trigiminal Nerve Electrostimulation-induced Reduction Of Seizures And Hippocampal Damage

AIM: Studies in animal and clinical have demonstrated the anti-epileptic and neuroprotective effects of trigiminal nerve electrostimulation(TNS). However, the mechanism of trigeminal nerve electrical stimulation(TNS) in reducing apoptosis, neuronal degeneration and neuron loss in the hippocampal is still unclear. The present study is aimed to investigate the role of anterior nucleus in trigeminal nerve electrostimulation(TNS)-induced effects on seizures and hippocampal damage using stereotactic lesion to the anterior thalamic nucleus.Methods: Healthy male Sprague-Dawley rats were randomly enrolled into the Control group(n=20),TNS group(n=25), Pilo group(n=25) and ATN group(n=25). Experimental rats including TNS group, Pilo group and ATN group were treated by intraperitoneal injection of pilocarpine to build status epilepticus(SE), after SE 30 min, then intraperitoneal injection of diazepam(10 mg/kg) to terminate the attack. The rats’ spontaneous seizures were observed by Video for a month to determine the establishment of chronic epilepsy model. Then rats received sham treatment, TNS treatment and TNS treatment after stereotactic lesion to anterior thalamic nucleus. The TNS treatment lasted for 1 month for each group. Another injection of pilo was conducted to induce seizure, and the severity and duration of seizure were quantitatively evaluated. And other rats were killed at different time(24h,48 h,72h,1w)after seizure. TUNEL, FJB and Nissl staining were applied to separately determine in situ apoptosis, neuronal degeneration and neuron loss in the hippocampal CA1 area and CA3 area.Results: 1. Trigeminal nerve electrical stimulation reduces seizures, and its antiepileptic effect after stereotactic lesion of the anterior thalamic nucleus was attenuated. Compared with Pilo group, TNS treatment significantly decreased the severity and duration of seizure(P<0.05). Compared with TNS group, TNS treatment after stereotactic lesion to anterior thalamic nucleus significantly increased the severity and duration of seizure(P<0.05). 2. Trigeminal nerve electrical stimulation decreases the number of TUNEL, FJB positive cells and neuron loss in the hippocampus, and its neuroprotective effect was attenuated after stereotactic lesion of the anterior thalamic nucleus. Compared with Pilo group, TNS treatment significantly decreased the number of TUNEL, FJB positive cells and neuron loss in the hippocampus(P<0.05). Compared with TNS group, TNS treatment after stereotactic lesion to anterior thalamic nucleus significantly increased the number of TUNEL, FJB positive cells and neuron loss in the hippocampus(P<0.05).Conclusion: Trigeminal nerve electrical stimulation can reduce seizures and hippocampus damage in chronic epilepsy rats. Anterior thalamic nucleus plays a role in TNS-induced reduction of seizures and hippocampus damage. The mechanisms might be due to the chronic activation of the cortex through ATN pathway induced by TNS, resulting in the downregulation of neuronal excitatory susceptibility.