How Is the Norepinephrine System Involved in the Antiepileptic Effects of Vagus Nerve Stimulation?

Abstract

Vagus Nerve Stimulation (VNS) is an adjunctive treatment for patients suffering from inoperable drug-resistant epilepsy. Although a complete understanding of the mediators involved in the antiepileptic effects of VNS and their complex interactions is lacking, VNS is known to trigger the release of neurotransmitters that have seizure-suppressing effects. In particular, norepinephrine (NE) is a neurotransmitter that has been associated with the clinical effects of VNS by preventing seizure development and by inducing long-term plastic changes that could restore a normal function of the brain circuitry. However, the biological requisites to become responder to VNS are still unknown. In this review, we report evidence of the critical involvement of NE in the antiepileptic effects of VNS in rodents and humans. Moreover, we emphasize the hypothesis that the functional integrity of the noradrenergic system could be a determining factor to obtain clinical benefits from the therapy. Finally, encouraging avenues of research involving NE in VNS treatment are discussed. These could lead to the personalization of the stimulation parameters to maximize the antiepileptic effects and potentially improve the response rate to the therapy.

Latest Views on the Mechanisms of Action of Surgically Implanted Cervical Vagal Nerve Stimulation in Epilepsy

“…A strong positive correlation was found between the noradrenergic and antiseizure effects of VNS. 48 Blockade of hippocampal α(2)receptors reversed the seizure-suppressing effect of VNS. 49 Other neurotransmitters such as GABA, glycine, and various amino-acid pools were found to be modified by VNS in the brain.…”

Effectiveness of Home Care Interventions in Patients with Moderate to Severe Craniocerebral Injury Combined with Epilepsy

“…With the current pharmaceutical technology, the treatment of epilepsy diseases mainly relies on medication, but patients can become somewhat dependent on medication. Vagus Nerve Stimulation (VNS) is a therapy option for patients with drug-resistant epilepsy who cannot get treatment [ 8 ]. Several researches conducted over the last few decades suggest that administering cannabinoids and activating the endocannabinoid system (ECS) are treatment methods for controlling epilepsy.…”

“…For patients with intractable focal epilepsy, surgical excision of the epileptogenic tissue is a well-established treatment option [7] With the current pharmaceutical technology, the treatment of epilepsy diseases mainly relies on medication, but patients can become somewhat dependent on medication. Vagus Nerve Stimulation (VNS) is a therapy option for patients with drug-resistant epilepsy who cannot get treatment [8]. Several researches conducted over the last few decades suggest that administering cannabinoids and activating the endocannabinoid system (ECS) are treatment Hindawi Computational and Mathematical Methods in Medicine Volume 2022, Article ID 3654181, 6 pages https://doi.org/10.1155/2022/3654181 methods for controlling epilepsy.…”

MRI-assessed locus coeruleus contrast and functional response are not associated in young and late middle-aged individuals

“…Aside from the early tauopathy of the LC that appears to contribute to AD (Jacobs et al, 2021), synucleinopathy contributing to LC degeneration was also detected in prodromal dementia of Lewis bodies (Hansen, 2021). Finally, concerning existing therapies targeting the LC-NE system, it was suggested that the functional integrity of this system may be linked to responsiveness to Vagus Nerve Stimulation in patients with inoperable drug-resistant epilepsy (Berger et al, 2021; de Taeye et al, 2014; Hödl et al, 2020). In the context of healthy aging, our results indicate that, while LC contrast changes with age, LC responsiveness may remain stable such that any abnormal response may constitute an early sign of an unhealthy trajectory.…”