The Anterior Thalamus Nucleus-Involved Mechanisms In The Alterations Of Excitatory Plasticity Induced By Trigeminal Nerve Stimulation

The anterior thalamus nucleus-involved mechanisms in the alterations of excitatory plasticity induced by trigeminal nerve stimulation Objective The expression of vesicular glutamate transporter 1(VGLUT1) and vesicular GABA transporter(VGAT) in the hippocampus and cortex induced by trigeminal nerve stimulation in chronic epileptic rats with or without pre-lesion to the anterior thalamus nucleus was observed, to explore the role of anterior thalamus nucleus(ATN) in the antiepileptic effect of trigeminal nerve stimulation in rats. Methods 100 healthy male SD rats were randomly divided into four groups: Control, Pilo, TNS and ATN group. In Pilo, TNS and ATN group rats, status epilepticus(SE) was firstly introduced by pilocarpine to induce chronic epilepsy, i.e. spontaneous recurrent seizures(SRS). As for the ATN rats, one week after the SE was established, ATN was conducted. Then all the rats in Pilo, TNS and ATN group were treated with trigeminal nerve stimulation or sham stimulation for one month after ATN group recovered from anterior thalamus nucleus lesions. The rats in the control group were treated with the same dose of normal saline. Then the rats were sacrificed at 24h、72h、14d、and 28 d post the end of trigeminal nerve stimulation. Finally, the expression of VGLUT1 and VGAT in hippocampus and cortex was examined with double immunofluorescence.Results(1) The average single cell expression level of VGLUT1 in the hippocampus and cortex in the ATN and TNS group rats was higher than that in the Control group, but the expression in both group rats were in a declining trend with time moving forward post-TNS. In TNS group, the expression of VGLUT1 in the hippocampus was higher than that in ATN group at 24 h, 72h(P<0.001, P<0.05), but lower at 14 d, 28 d,(P<0.05). And the expression of VGLUT1 in cortex was higher than that in ATN group at 24 h, 72h(P<0.05), but lower at 7d,14 d, 28 d,(P<0.05).(2) The expression of VGAT was similar to VGLUT1. The average single cell expression level of VGAT in TNS and ATN group rats’ hippocampus was higher than that in Control group, and their expression also showed a trend of decline post-TNS. But the expression of VGAT in TNS group was higher than that in ATN group at all the time points post-TNS(P<0.001,P<0.05). Conclusion Anterior thalamic nucleus lesion may reduce the chronic trigeminal nerve stimulation-induced chronic activation of the cortex and hippocampus, affecting these neuronal excitatory pre-adaptation induced by chronic trigeminal nerve stimulation, thus hindering the increasement of excitability threshold, eventually reducing the antiepileptic effects of chronic trigeminal nerve stimulation.