Regulation of Limbic Motor Seizures by GABA and Glutamate Transmission in Nucleus Tractus Solitarius

Walker, Benjimen R.; Easton, Amy; Gale, Karen

doi:10.1111/j.1528-1157.1999.tb00818.x

Cited by 139 publications

(68 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[5][6][7] The anatomy and biology of the trigeminal nerve support potential mechanisms by which TNS may impact epilepsy and mood disorders, and animal data demonstrate that stimulation of the trigeminal nerve and its related structures inhibits seizures. [8][9][10][11][12][13][14][15][16][17] In a rat pentylenetetrazole model, TNS resulted in reductions in the number of seizures (range 236% to 58%) depending on stimulus intensity. 11,12 The magnitude of the seizure-reduction effect increased as the amplitude and frequency of stimulation increased, and bilateral stimulation was more effective than unilateral stimulation.…”

mentioning

confidence: 99%

Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy

et al. 2013

View full text Add to dashboard Cite

Objective: To explore the safety and efficacy of external trigeminal nerve stimulation (eTNS) in patients with drug-resistant epilepsy (DRE) using a double-blind randomized controlled trial design, and to test the suitability of treatment and control parameters in preparation for a phase III multicenter clinical trial.Methods: This is a double-blind randomized active-control trial in DRE. Fifty subjects with 2 or more partial onset seizures per month (complex partial or tonic-clonic) entered a 6-week baseline period, and then were evaluated at 6, 12, and 18 weeks during the acute treatment period. Subjects were randomized to treatment (eTNS 120 Hz) or control (eTNS 2 Hz) parameters.Results: At entry, subjects were highly drug-resistant, averaging 8.7 seizures per month (treatment group) and 4.8 seizures per month (active controls). On average, subjects failed 3.35 antiepileptic drugs prior to enrollment, with an average duration of epilepsy of 21.5 years (treatment group) and 23.7 years (active control group), respectively. eTNS was well-tolerated. Side effects included anxiety (4%), headache (4%), and skin irritation (14%). The responder rate, defined as .50% reduction in seizure frequency, was 30.2% for the treatment group vs 21.1% for the active control group for the 18-week treatment period (not significant, p 5 0.31, generalized estimating equation [GEE] model). The treatment group experienced a significant within-group improvement in responder rate over the 18-week treatment period (from 17.8% at 6 weeks to 40.5% at 18 weeks, p 5 0.01, GEE). Subjects in the treatment group were more likely to respond than patients randomized to control (odds ratio 1.73, confidence interval 0.59-0.51). eTNS was associated with reductions in seizure frequency as measured by the response ratio (p 5 0.04, analysis of variance [ANOVA]), and improvements in mood on the Beck Depression Inventory (p 5 0.02, ANOVA). Conclusions:This study provides preliminary evidence that eTNS is safe and may be effective in subjects with DRE. Side effects were primarily limited to anxiety, headache, and skin irritation. These results will serve as a basis to inform and power a larger multicenter phase III clinical trial. Drug-resistant epilepsy (DRE) affects 30% of all people with epilepsy, and may lead to disability and death. [1][2][3][4] Trigeminal nerve stimulation (TNS) is a novel investigational neuromodulation therapy for patients with DRE. Classification of evidence:5 TNS can be delivered noninvasively, bilaterally, and at high frequencies, with positive effects on mood.5-7 The anatomy and biology of the trigeminal nerve support potential mechanisms by which TNS may impact epilepsy and mood disorders, and animal data demonstrate that stimulation of the trigeminal nerve and its related structures

show abstract

mentioning

confidence: 99%

Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The effects seen with bicuculline in some central nervous system systems appear to be due to unopposed influence of the major excitatory neurotransmitter Lglutamate (49). Therefore, preliminary studies were undertaken that tested the hypothesis that bicuculline-induced apnea was caused by unopposed L-glutamate exciting neurons in the vlNTS.…”

Section: Effects Of Unilateral Microinjection Of Kynurenic Acid Into mentioning

confidence: 99%

GABA-mediated neurotransmission in the ventrolateral NTS plays a role in respiratory regulation in the rat

Wasserman

Ferreira

Sahibzada

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

. GABA-mediated neurotransmission in the ventrolateral NTS plays a role in respiratory regulation in the rat. Am J Physiol Regul Integr Comp Physiol 283: R1423-R1441, 2002 10.1152/ ajpregu.00488.2001.-Our purpose was to determine whether endogenously released GABA in the ventrolateral nucleus of the solitary tract (vlNTS) of the rat influences respiration. Experiments were carried out in anesthetized, vagotomized and spontaneously breathing rats, and diaphragm electromyogram activity was measured while drugs affecting GABAergic neurotransmission were microinjected into the vlNTS and medial NTS (mNTS). Bilateral microinjection of nipecotic acid, 5 or 25 nmol, into the vlNTS (but not in the mNTS) produced dose-dependent increases in inspiratory duration (TI) frequently culminating in apneustic breathing. Neither unilateral microinjection of bicuculline nor CGP-35348 (GABA B receptor antagonist) reversed this response; however, a combination of both GABA receptor antagonists effectively reversed apneustic breathing. Bilateral microinjection of either muscimol or baclofen into the vlNTS mimicked the effect of nipecotic acid. Microinjection of the bicuculline produced apnea, whereas microinjection of CGP-35348 produced a decrease in TI and an increase in expiratory duration. Immunohistochemical analysis of the vlNTS region revealed GABA A receptors densely localized to processes, whereas GABA B immunoreactivity was localized to cell bodies. Our data indicate that GABA activity in the vlNTS is important for respiratory function. apneusis; apnea; inspiratory off-switch WE RECENTLY REPORTED that neurons in the region of the ventrolateral nucleus of the solitary tract (vlNTS) of the rat have an important role in the control of respiratory function (50). Our hypothesis was that these neurons act as part of the "inspiratory off-switch" (IOS) and terminate the inspiratory phase of the respiratory cycle. This was tested using drugs that hyperpolarize (GABA), disfacilitate (kynurenic acid), and block both axonal conduction and action potential generation (tetrodotoxin). These drugs were used as tools to ascertain the function of the vlNTS and were not used to delineate the neurotransmitter systems involved. Bilateral microinjection of each of these agents prolonged inspiratory duration (TI) and evoked an apneustic pattern of breathing. These results supported our hypothesis that neurons in the region of the vlNTS promote the transition from inspiration to expiration and function as part of the IOS.As vlNTS neurons appear to function as an integral part of the IOS in the rat, we next focused our attention on the question of which central nervous system neurotransmitter systems control the level of activity of these neurons. Recent data of Ellenberger (11) suggest a widespread role for GABAergic regulation of respiratory function within respiratory-related portions of the NTS (e.g., ventrolateral, interstitial, and commissural subnuclei). This was demonstrated for glutamic acid decarboxylase (GAD) immunohistochemistry. Relati...

show abstract

“…serotonin, norepinephrine, GABA, and glutamate [17][18][19][20][21] . Neuroimaging studies with SPECT, PET, and functional MRI demonstrate that VNS induces changes in regional cerebral blood flow (rCBF) similar to those seen with antidepressants [22][23][24] ; either in the amygdala or in the hippocampus or parahippocampus [14] .…”

Section: Neurobiology Of Vnsmentioning

confidence: 99%

The Application of Vagus Nerve Stimulation and Deep Brain Stimulation in Depression

Mohr

Rodríguez

A³

et al. 2011

Neuropsychobiology

View full text Add to dashboard Cite

Despite the progress in the pharmacotherapy of depression, there is a substantial proportion of treatment-resistant patients. Recently, reversible invasive stimulation methods, i.e. vagus nerve stimulation (VNS) and deep brain stimulation (DBS), have been introduced into the management of treatment-resistant depression (TRD). VNS has already received regulatory approval for TRD. This paper reviews the available clinical evidence and neurobiology of VNS and DBS in TRD. The principle of VNS is a stimulation of the left cervical vagus nerve with a programmable neurostimulator. VNS was examined in 4 clinical trials with 355 patients. VNS demonstrated steadily increasing improvement with full benefit after 6–12 months, sustained up to 2 years. Patients who responded best had a low-to-moderate antidepressant resistance. However, the primary results of the only controlled trial were negative. DBS involves stereotactical implantation of electrodes powered by a pulse generator into the specific brain regions. For depression, the targeted areas are the subthalamic nucleus, internal globus pallidus, ventral internal capsule/ventral striatum, the subgenual cingulated region, and the nucleus accumbens. Antidepressant effects of DBS were examined in case series with a total number of 50 TRD patients. Stimulation of different brain regions resulted in a reduction of depressive symptoms. The clinical data on the use of VNS and DBS in TRD are encouraging. The major contribution of the methods is a novel approach that allows for precise targeting of the specific brain areas, nuclei and circuits implicated in the etiopathogenesis of neuropsychiatric disorders. For clinical practice, it is necessary to identify patients who may best benefit from VNS or DBS.

show abstract

Regulation of Limbic Motor Seizures by GABA and Glutamate Transmission in Nucleus Tractus Solitarius

Cited by 139 publications

References 44 publications

Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy

Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy

GABA-mediated neurotransmission in the ventrolateral NTS plays a role in respiratory regulation in the rat

The Application of Vagus Nerve Stimulation and Deep Brain Stimulation in Depression

Contact Info

Product

Resources

About