Trigeminal Nerve Electrical Stimulation: An Effective Arousal Treatment For Loss Of Consciousness

Background: To determine if trigeminal nerve electrical stimulation (TNS) would be an effective arousal treatment for loss of consciousness (LOC), we applied neuroscientific methods to investigate the role of potential brain circuit and neuropeptide pathway in regulating level of consciousness.Methods: Consciousness behavioral analysis, Electroencephalogram (EEG) recording, Chemogenetics, Micmarray analysis, Milliplex MAP rat peptide assay, Chromatin immune-precipitation (ChIP), Dual-luciferase reporter experiment, Western blot, PCR and Fluorescence in situ hybridization (FISH).Results: TNS can markedly activate the neuronal activities of the lateral hypothalamus (LH) and the spinal trigeminal nucleus (Sp5), as well as improve rat consciousness level and EEG activities. Then we proved that LH activation and upregulated neuropeptide hypocretin are beneficial for promotion of consciousness recovery. We then applied gene micmarray experiment and found hypocretin might be mediated by a well-known transcription factor Early growth response gene 1 (EGR1), and the results were confirmed by ChIP and Dual-luciferase reporter experiment.Conclusion: This study illustrates that TNS is an effective arousal strategy Treatment for LOC state via the activation of Sp5 and LH neurons and upregulation of hypocretin expression.