Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain

Follesa, Paolo; Biggio, Francesca; Gorini, Giorgio; Caria, Stefania; Talani, Giuseppe; Dazzi, Laura; Puligheddu, Monica; Marrosu, Francesco; Biggio, Giovanni

doi:10.1016/j.brainres.2007.08.045

Cited by 304 publications

(223 citation statements)

References 54 publications

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“…Among these, Smith et al, 2006 suggested that the therapeutic effects of VNS for the treatment of animals subjected to traumatic brain injury were due to enhanced noradrenergic activity. Other studies demonstrated increased activity of the noradrenergic locus coeruleus (LC) and central levels of norepinephrine following VNS as well as a reduction of VNS-induced seizure attenuation following LC lesions (Krahl et al, 1998;Groves et al, 2005;Roosevelt et al, 2006;Follesa et al, 2007). More recently, Raedt et al (2011) further demonstrated that VNS-induced increases in norepinephrine release correlate with acute anti-seizure efficacy.…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors

et al. 2011

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Abstract-Vagus nerve stimulation (VNS) is an FDA approved treatment for drug-resistant epilepsy and depression.Recently, we demonstrated the capacity for repeatedly pairing sensory input with brief pulses of VNS to induce input specific reorganization in rat auditory cortex. This was subsequently used to reverse the pathological neural and perceptual correlates of hearing loss induced tinnitus. Despite its therapeutic potential, VNS mechanisms of action remain speculative. In this study, we report the acute effects of VNS on intra-cortical synchrony, excitability, and sensory processing in anesthetized rat auditory cortex. VNS significantly increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 -8 Hz but not after application of the muscarinic antagonist scopolamine. Collectively, these experiments demonstrate the capacity for VNS to acutely influence cortical synchrony and excitability and strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in VNS mechanisms of action. These results are discussed with respect to their possible implications for sensory processing, neural plasticity, and epilepsy.

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Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors

et al. 2011

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“…In addition, the basal firing rate in the LC is significantly increased after long-term treatment with VNS [46]. In rats, VNS induces an increase of NE concentration in the hippocampus [47], the amygdala [48], and the cerebral cortex [47,49]. Moreover, lesions of the LC block the anticonvulsant effect of VNS [50].…”

Section: Discussionmentioning

confidence: 99%

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

et al. 2014

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Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient's response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (>50 %) and 10 nonresponders (≤50 %). Two stimulation conditions were compared: VNS OFF and VNS ON. In each condition, the P3 component was measured during an auditory oddball paradigm. VNS induced a significant increase of the P3 amplitude at the parietal midline electrode, in VNS responders only. In addition, logistic regression analysis showed that the increase of P3 amplitude can be used as a noninvasive indicator for VNS responders. These results support the hypothesis that activation of the locus coeruleus noradrenergic system is associated with the antiepileptic effect of VNS. Modulation of the P3 amplitude should be further investigated as a noninvasive biomarker for the therapeutic efficacy of VNS in patients with refractory epilepsy.

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“…VNS increases levels of brain-derived neurotrophic factor (BDNF), a key regulator of plasticity [17]. BDNF activates multiple downstream effector elements associated with synaptic plasticity, including cyclic adenosine monophosphate response element binding protein, activity-regulated cytoskeletal protein (Arc), and CaMKII [141][142][143][144].…”

Section: Identifying Mechanisms That Underlie Recoverymentioning

confidence: 99%

“…While most often recognized for its descending projections to viscera, > 80 % of the vagus nerve consists of afferent connections that terminate in the nucleus tractus solitarius in the brainstem [11][12][13][14]. Electrical stimulation of the vagus nerve drives activity in the cholinergic basal forebrain and the noradrenergic locus coeruleus, and results in subsequent release of neuromodulators throughout the cortex [15][16][17][18][19][20]. A reduction in either noradrenergic or cholinergic transmission blocks the effects of VNS in the CNS [21,22].…”

Section: Introductionmentioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

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Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain

Cited by 304 publications

References 54 publications

Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors

Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

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