Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke
Navid Khodaparast, Seth A Hays, Andrew M Sloan, Tabbassum Fayyaz, Daniel R Hulsey, Robert L Rennaker 2nd, Michael P Kilgard, Navid Khodaparast, Seth A Hays, Andrew M Sloan, Tabbassum Fayyaz, Daniel R Hulsey, Robert L Rennaker 2nd, Michael P Kilgard
Abstract
Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation.
Keywords: cortical ischemia; motor cortex; plasticity; recovery; rehabilitation; stroke.
© The Author(s) 2014.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4134702/bin/nihms-553415-f0001.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4134702/bin/nihms-553415-f0002.jpg)
Figure 3
Schematic representations of the smallest,…
Figure 3
Schematic representations of the smallest, representative, and largest lesion following intracortical ET-1 infarct.…
Figure 4
Inter-press interval on the bradykinesia…
Figure 4
Inter-press interval on the bradykinesia assessment task. Using the bradykinesia assessment task, forelimb…
Figure 5
A) Individual rat performance on…
Figure 5
A) Individual rat performance on the bradykinesia assessment task. Symbols indicate when an…
- Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.Khodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL 2nd, Kilgard MP. Khodaparast N, et al. Neurobiol Dis. 2013 Dec;60:80-8. doi: 10.1016/j.nbd.2013.08.002. Epub 2013 Aug 15. Neurobiol Dis. 2013. PMID: 23954448
- Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats.Khodaparast N, Kilgard MP, Casavant R, Ruiz A, Qureshi I, Ganzer PD, Rennaker RL 2nd, Hays SA. Khodaparast N, et al. Neurorehabil Neural Repair. 2016 Aug;30(7):676-84. doi: 10.1177/1545968315616494. Epub 2015 Nov 4. Neurorehabil Neural Repair. 2016. PMID: 26542082 Free PMC article.
- Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats.Hays SA, Ruiz A, Bethea T, Khodaparast N, Carmel JB, Rennaker RL 2nd, Kilgard MP. Hays SA, et al. Neurobiol Aging. 2016 Jul;43:111-8. doi: 10.1016/j.neurobiolaging.2016.03.030. Epub 2016 Apr 7. Neurobiol Aging. 2016. PMID: 27255820 Free PMC article.
- Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke.Engineer ND, Kimberley TJ, Prudente CN, Dawson J, Tarver WB, Hays SA. Engineer ND, et al. Front Neurosci. 2019 Mar 29;13:280. doi: 10.3389/fnins.2019.00280. eCollection 2019. Front Neurosci. 2019. PMID: 30983963 Free PMC article. Review.
- Recovery of motor function after stroke.Brown JA. Brown JA. Prog Brain Res. 2006;157:223-8. doi: 10.1016/S0079-6123(06)57015-3. Prog Brain Res. 2006. PMID: 17046674 Review.
- Research Support, Non-U.S. Gov't
- Animals
- Brain Ischemia / rehabilitation*
- Disease Models, Animal
- Female
- Hypokinesia / rehabilitation
- Motor Activity
- Motor Cortex / pathology
- Physical Conditioning, Animal*
- Rats
- Rats, Sprague-Dawley
- Recovery of Function*
- Stroke Rehabilitation*
- Vagus Nerve Stimulation*
- Full Text Sources
- Other Literature Sources
- Medical
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![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4134702/bin/nihms-553415-f0003.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4134702/bin/nihms-553415-f0004.jpg)
Figure 5
A) Individual rat performance on…
Figure 5
A) Individual rat performance on the bradykinesia assessment task. Symbols indicate when an…
- Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.Khodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL 2nd, Kilgard MP. Khodaparast N, et al. Neurobiol Dis. 2013 Dec;60:80-8. doi: 10.1016/j.nbd.2013.08.002. Epub 2013 Aug 15. Neurobiol Dis. 2013. PMID: 23954448
- Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats.Khodaparast N, Kilgard MP, Casavant R, Ruiz A, Qureshi I, Ganzer PD, Rennaker RL 2nd, Hays SA. Khodaparast N, et al. Neurorehabil Neural Repair. 2016 Aug;30(7):676-84. doi: 10.1177/1545968315616494. Epub 2015 Nov 4. Neurorehabil Neural Repair. 2016. PMID: 26542082 Free PMC article.
- Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats.Hays SA, Ruiz A, Bethea T, Khodaparast N, Carmel JB, Rennaker RL 2nd, Kilgard MP. Hays SA, et al. Neurobiol Aging. 2016 Jul;43:111-8. doi: 10.1016/j.neurobiolaging.2016.03.030. Epub 2016 Apr 7. Neurobiol Aging. 2016. PMID: 27255820 Free PMC article.
- Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke.Engineer ND, Kimberley TJ, Prudente CN, Dawson J, Tarver WB, Hays SA. Engineer ND, et al. Front Neurosci. 2019 Mar 29;13:280. doi: 10.3389/fnins.2019.00280. eCollection 2019. Front Neurosci. 2019. PMID: 30983963 Free PMC article. Review.
- Recovery of motor function after stroke.Brown JA. Brown JA. Prog Brain Res. 2006;157:223-8. doi: 10.1016/S0079-6123(06)57015-3. Prog Brain Res. 2006. PMID: 17046674 Review.
- Research Support, Non-U.S. Gov't
- Animals
- Brain Ischemia / rehabilitation*
- Disease Models, Animal
- Female
- Hypokinesia / rehabilitation
- Motor Activity
- Motor Cortex / pathology
- Physical Conditioning, Animal*
- Rats
- Rats, Sprague-Dawley
- Recovery of Function*
- Stroke Rehabilitation*
- Vagus Nerve Stimulation*
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4134702/bin/nihms-553415-f0005.jpg)
Source: PubMed