Stroke is a leading cause of disability, with an estimated 795,000 cases reported in the US each year. As many as 70% of patients who suffer a stroke display a long-term impairment in upper extremity motor function. Many stroke patients exhibit associated risk factors which can impair recovery of function, such as advanced age. The development of rehabilitative strategies to improve the recovery of motor function in the context of advanced age is of key importance. We propose to evaluate a novel early stage therapy to improve stroke recovery which utilizes stimulation of the vagus nerve paired with rehabilitative training. Pairing vagus nerve stimulation (VNS) with movement results in highly specific, long-lasting neuroplasticity in rat primary motor cortex. Furthermore, VNS delivered during rehabilitation improves recovery of forelimb speed and strength after an ischemic lesion of the motor cortex in young adult rats. To evaluate if VNS paired with physical rehabilitation may be useful in stroke patients, we propose to test the therapy in a model that more accurately represents the clinical population. Because advanced age is a leading risk factor for stroke and may limit plasticity, the experiments described in this proposal will evaluate VNS in a model of stroke at an advanced age.
The first aim of the study will assess the ability of VNS paired with rehabilitative training to improve recovery of motor function after ischemic stroke in aged rats.
The second aim of this proposal will examine structural plasticity mechanisms that underlie recovery after stroke.
The third aim of the study will assess the ability of VNS paired with physical training to enhance map plasticity in motor cortex of aged rats. We hypothesize that in aged rats, VNS paired with physical training will result in improved recovery of function, increased structural plasticity, and enhanced map plasticity beyond physical training alone. The results of the proposed experiments will clarify the relationship between advanced age and recovery of motor function are stroke. Insights from these studies will help to delineate the clinical population for which VNS paired with physical rehabilitation is likely to confer therapeutc benefits and improve the likelihood of successful translation of the therapy.

Public Health Relevance

Stroke is a leading cause of disability in the US and often occurs in patients of advanced age. The proposed study will evaluate the effectiveness of vagus nerve stimulation paired with physical rehabilitation to enhance neuroplasticity and recovery in a model of ischemic stroke in aged rats. An improved understanding of how advanced age, which is common in stroke patients, affects vagus nerve stimulation paired with physical rehabilitation will improve the likelihood of successful implementation of the therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS085167-01A1
Application #
8761816
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Chen, Daofen
Project Start
2014-07-01
Project End
2019-04-30
Budget Start
2014-07-01
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas-Dallas
Department
Type
Other Specialized Schools
DUNS #
City
Richardson
State
TX
Country
United States
Zip Code
75080
Morrison, Robert A; Hulsey, Daniel R; Adcock, Katherine S et al. (2018) Vagus nerve stimulation intensity influences motor cortex plasticity. Brain Stimul :
Loerwald, Kristofer W; Borland, Michael S; Rennaker 2nd, Robert L et al. (2018) The interaction of pulse width and current intensity on the extent of cortical plasticity evoked by vagus nerve stimulation. Brain Stimul 11:271-277
Borland, Michael S; Engineer, Crystal T; Vrana, William A et al. (2018) The Interval Between VNS-Tone Pairings Determines the Extent of Cortical Map Plasticity. Neuroscience 369:76-86
Ganzer, Patrick D; Darrow, Michael J; Meyers, Eric C et al. (2018) Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury. Elife 7:
Meyers, Eric C; Solorzano, Bleyda R; James, Justin et al. (2018) Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery. Stroke 49:710-717
Engineer, Crystal T; Hays, Seth A; Kilgard, Michael P (2017) Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders. J Neurodev Disord 9:20
Pruitt, David T; Danaphongse, Tanya T; Schmid, Ariel N et al. (2017) Traumatic Brain Injury Occludes Training-Dependent Cortical Reorganization in the Contralesional Hemisphere. J Neurotrauma 34:2495-2503
Engineer, Crystal T; Shetake, Jai A; Engineer, Navzer D et al. (2017) Temporal plasticity in auditory cortex improves neural discrimination of speech sounds. Brain Stimul 10:543-552
Meyers, Eric C; Granja, Rafael; Solorzano, Bleyda R et al. (2017) Median and ulnar nerve injuries reduce volitional forelimb strength in rats. Muscle Nerve 56:1149-1154
Hulsey, Daniel R; Riley, Jonathan R; Loerwald, Kristofer W et al. (2017) Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation. Exp Neurol 289:21-30

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