Enhancing plasticity in central networks improves motor and sensory recovery after nerve damage

Meyers, Eric; Kasliwal, Nimit; Solorzano, Bleyda R.; Lai, Elaine; Bendale, Geetanjali; Berry, Abigail; Ganzer, Patrick D.; Romero-Ortega, Mario I.; Rennaker, Robert L.; Kilgard, Michael P.; Hays, Seth A.

doi:10.1038/s41467-019-13695-0

Cited by 75 publications

(83 citation statements)

References 70 publications

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“…Delivery of VNS paired with rehabilitative training significantly enhanced recovery compared to equivalent training without VNS, providing a preliminary demonstration that VNS therapy can improve motor function after ICH (Figure 1C). Emerging evidence extends these findings to other distinct forms of neurological damage, indicating VNS can improve recovery in models of traumatic brain injury (Pruitt et al, 2016), spinal cord injury (SCI; Ganzer et al, 2018), and peripheral nerve damage (Meyers E. et al, 2018; Figure 2).…”

Section: Vns Improves Motor Function In Animal Models Of Strokementioning

confidence: 74%

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke

et al. 2019

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Stroke is a leading cause of disability worldwide, and in approximately 60% of individuals, upper limb deficits persist 6 months after stroke. These deficits adversely affect the functional use of the upper limb and restrict participation in day to day activities. An important goal of stroke rehabilitation is to improve the quality of life by enhancing functional independence and participation in activities. Since upper limb deficits are one of the best predictors of quality of life after stroke, effective interventions targeting these deficits may represent a means to improve quality of life. An increased understanding of the neurobiological processes underlying stroke recovery has led to the development of targeted approaches to improve motor deficits. One such targeted strategy uses brief bursts of Vagus Nerve Stimulation (VNS) paired with rehabilitation to enhance plasticity and support recovery of upper limb function after chronic stroke. Stimulation of the vagus nerve triggers release of plasticity promoting neuromodulators, such as acetylcholine and norepinephrine, throughout the cortex. Timed engagement of neuromodulators concurrent with motor training drives task-specific plasticity in the motor cortex to improve function and provides the basis for paired VNS therapy. A number of studies in preclinical models of ischemic stroke demonstrated that VNS paired with rehabilitative training significantly improved the recovery of forelimb motor function compared to rehabilitative training without VNS. The improvements were associated with synaptic reorganization of cortical motor networks and recruitment of residual motor neurons controlling the impaired forelimb, demonstrating the putative neurobiological mechanisms underlying recovery of motor function. These preclinical studies provided the basis for conducting two multi-site, randomized controlled pilot trials in individuals with moderate to severe upper limb weakness after chronic ischemic stroke. In both studies, VNS paired with rehabilitation improved motor deficits compared to rehabilitation alone. The trials provided support for a 120-patient pivotal study designed to evaluate the efficacy of paired VNS therapy in individuals with chronic ischemic stroke. This manuscript will discuss the neurobiological rationale for VNS therapy, provide an in-depth discussion of both animal and human studies of VNS therapy for stroke, and outline the challenges and opportunities for the future use of VNS therapy.

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Section: Vns Improves Motor Function In Animal Models Of Strokementioning

confidence: 74%

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke

et al. 2019

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“…Electrical stimulation of peripheral autonomic nerves has the potential to treat conditions in which the nervous system is affected or implicated. For example, vagus nerve stimulation (VNS) has been approved for certain forms of epilepsy 1,2 and depression 3 and is being tested in the treatment of heart failure 4,5 , rheumatoid arthritis 6 , lupus 7 , inflammatory bowel disease 8 , pulmonary hypertension 9 , arrhythmias 10 , neurorehabilitation 11 , etc. The cervical vagus is an important clinical target for invasive neuromodulation, as it is easily accessible surgically and requires a minor operation for electrode implantation 12,13 .…”

Section: Vagus Nerve Stimulation (Vns) Is a Bioelectronic Therapy Formentioning

confidence: 99%

Anodal block permits directional vagus nerve stimulation

Ahmed

Chang

Cracchiolo

et al. 2020

Sci Rep

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“…Synaptic plasticity resulting from vagus nerve stimulation pairing is known to involve multiple neuromodulatory systems, including acetylcholine, norepinephrine, and serotonin [17,18,41]. Depletion of these neuromodulators prevents VNS-dependent plasticity and subsequently abolishes the benefits of VNS therapy [17,18,42]. However, neuromodulator release is known to be disrupted in both Mecp2 rodents and individuals with Rett syndrome [12,24,25,43e46].…”

Section: The Neuromodulatory Systems In Rett Syndromementioning

confidence: 99%

Vagus nerve stimulation paired with tones restores auditory processing in a rat model of Rett syndrome

Adcock¹,

Chandler²,

Buell³

et al. 2020

Brain Stimulation

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Background: Rett syndrome is a rare neurological disorder associated with a mutation in the X-linked gene MECP2. This disorder mainly affects females, who typically have seemingly normal early development followed by a regression of acquired skills. The rodent Mecp2 model exhibits many of the classic neural abnormalities and behavioral deficits observed in individuals with Rett syndrome. Similar to individuals with Rett syndrome, both auditory discrimination ability and auditory cortical responses are impaired in heterozygous Mecp2 rats. The development of therapies that can enhance plasticity in auditory networks and improve auditory processing has the potential to impact the lives of individuals with Rett syndrome. Evidence suggests that precisely timed vagus nerve stimulation (VNS) paired with sound presentation can drive robust neuroplasticity in auditory networks and enhance the benefits of auditory therapy. Objective: The aim of this study was to investigate the ability of VNS paired with tones to restore auditory processing in Mecp2 transgenic rats. Methods: Seventeen female heterozygous Mecp2 rats and 8 female wild-type (WT) littermates were used in this study. The rats were exposed to multiple tone frequencies paired with VNS 300 times per day for 20 days. Auditory cortex responses were then examined following VNS-tone pairing therapy or no therapy. Results: Our results indicate that Mecp2 mutation alters auditory cortex responses to sounds compared to WT controls. VNS-tone pairing in Mecp2 rats improves the cortical response strength to both tones and speech sounds compared to untreated Mecp2 rats. Additionally, VNS-tone pairing increased the information contained in the neural response that can be used to discriminate between different consonant sounds. Conclusion:These results demonstrate that VNS-sound pairing may represent a strategy to enhance auditory function in individuals with Rett syndrome.

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Enhancing plasticity in central networks improves motor and sensory recovery after nerve damage

Cited by 75 publications

References 70 publications

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke

Anodal block permits directional vagus nerve stimulation

Vagus nerve stimulation paired with tones restores auditory processing in a rat model of Rett syndrome

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