| Objective: To investigate the effects of trigeminal nerve stimulation (TNS) on hippocampal neuronal apoptosis and the expression of glutamate transporter 1 (GLT1) in rats with global cerebral ischemia. Methods: Fifty rats were randomly divided into five groups: Sham group, cerebral ischemia (CI) group, trigeminal nerve stimulation (TNS) group, and Caspase-3-specific inhibitor Z-DEVD-FMK (FMK) group. A global cerebral ischemia-hypoxia model was established using bilateral common carotid artery occlusion. After intraperitoneal injection of 1% sodium pentobarbital (40 mg/kg body weight), TNS and FMK groups were implanted with trigeminal ganglion stimulation electrodes. Electrical stimulation parameters included square wave pulses at a frequency of 5 Hz, current intensity of 0.5–1 mA, and stimulation duration of 15 minutes. In the TNS and FMK groups, the first stimulation was administered 30 minutes after successful modeling, followed by one stimulation every 6 hours for a total of four sessions. After 24 hours, the rats were decapitated, and the hippocampal CA1 region was rapidly isolated. Neuronal apoptosis in the CA1 region was detected using TUNEL in situ end-labeling, while Western blot analysis was performed to examine the expression of GLT1, Bax, Bcl-2, and Caspase-3 proteins. Results: Compared to the Sham group, the apoptosis index was significantly increased in the CI, TNS, and FMK groups. However, the TNS group showed a significant reduction in the apoptosis index compared to the CI group, with statistically significant differences between the groups (P<0.05). Compared to the Sham group, the CI group exhibited increased expression of Bax and Caspase-3 and decreased expression of GLT1 and Bcl-2 in the hippocampal CA1 region (P<0.05). In contrast, the TNS group showed downregulation of Bax and Caspase-3 and upregulation of GLT1 and Bcl-2 compared to the CI group (P<0.05). However, no significant differences were observed in the expression of Bax, Bcl-2, and Caspase-3 between the CI and FMK groups (P>0.05). Conclusion: The arousal-promoting effect of TNS in global cerebral ischemia-induced coma may be associated with the upregulation of GLT1 expression mediated by the Bax/Bcl-2/Caspase-3 signaling pathway, leading to reduced neuronal apoptosis in the hippocampal CA1 region. |
