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Optimizing Dosing of Vagus Nerve Stimulation for Stroke Recovery.

Abstract
Vagus nerve stimulation (VNS) paired with rehabilitative training enhances recovery of function in models of stroke and is currently under investigation for use in chronic stroke patients. Dosing is critical in translation of pharmacological therapies, but electrical stimulation therapies often fail to comprehensively explore dosing parameters in preclinical studies. Varying VNS parameters has non-monotonic effects on plasticity in the central nervous system, which may directly impact efficacy for stroke. We sought to optimize stimulation intensity to maximize recovery of motor function in a model of ischemic stroke. The study design was preregistered prior to beginning data collection (DOI: https://doi.org/10.17605/OSF.IO/BMJEK ). After training on an automated assessment of forelimb function and receiving an ischemic lesion in motor cortex, rats were separated into groups that received rehabilitative training paired with VNS at distinct stimulation intensities (sham, 0.4 mA, 0.8 mA, or 1.6 mA). Moderate-intensity VNS at 0.8 mA enhanced recovery of function compared with all other groups. Neither 0.4 mA nor 1.6 mA VNS was sufficient to improve functional recovery compared with equivalent rehabilitation without VNS. These results demonstrate that moderate-intensity VNS delivered during rehabilitation improves recovery and defines an optimized intensity paradigm for clinical implementation of VNS therapy.
AuthorsDavid T Pruitt, Tanya T Danaphongse, Megan Lutchman, Nishi Patel, Priyanka Reddy, Vanesse Wang, Anjana Parashar, Robert L Rennaker 2nd, Michael P Kilgard, Seth A Hays
JournalTranslational stroke research (Transl Stroke Res) Vol. 12 Issue 1 Pg. 65-71 (02 2021) ISSN: 1868-601X [Electronic] United States
PMID32583333 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Topics
  • Animals
  • Female
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function (physiology)
  • Stroke (diagnosis, physiopathology, therapy)
  • Stroke Rehabilitation (methods, standards)
  • Vagus Nerve Stimulation (methods, standards)

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