Carolina Cywiak1, Ryan C Ashbaugh2, Abigael C Metto1, Lalita Udpa3, Chunqi Qian4, Assaf A Gilad5, Mark Reimers6, Ming Zhong7, Galit Pelled8. 1. Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA; The Institute of Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA. 2. The Institute of Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI, USA. 3. Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI, USA. 4. Department of Radiology, Michigan State University, East Lansing, MI, USA. 5. Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA; The Institute of Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Radiology, Michigan State University, East Lansing, MI, USA. 6. The Institute of Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Physiology and Neuroscience Program, Michigan State University, East Lansing, MI, USA. 7. The Institute of Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA. 8. Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA; The Institute of Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Radiology, Michigan State University, East Lansing, MI, USA. Electronic address: pelledga@msu.edu.
Abstract
BACKGROUND: Twenty million Americans suffer from peripheral nerve injury. These patients often develop chronic pain and sensory dysfunctions. In the past decade, neuroimaging studies showed that these changes are associated with altered cortical excitation-inhibition balance and maladaptive plasticity. We tested if neuromodulation of the deprived sensory cortex could restore the cortical balance, and whether it would be effective in alleviating sensory complications. OBJECTIVE: We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which induces neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from glass catfish and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. METHODS: A rat model of forepaw denervation was used. rTMS was delivered every other day for 30 days, starting at the acute or at the chronic post-injury phase. A minimally-invasive neuromodulation via EPG was performed every day for 30 days starting at the chronic phase. A battery of behavioral tests was performed in the days and weeks following limb denervation in EPG-treated rats, and behavioral tests, fMRI and immunochemistry were performed in rTMS-treated rats. RESULTS: The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The results identify that both acute and delayed rTMS intervention facilitated rehabilitation. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. CONCLUSION: Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.
BACKGROUND: Twenty million Americans suffer from peripheral nerve injury. These patients often develop chronic pain and sensory dysfunctions. In the past decade, neuroimaging studies showed that these changes are associated with altered cortical excitation-inhibition balance and maladaptive plasticity. We tested if neuromodulation of the deprived sensory cortex could restore the cortical balance, and whether it would be effective in alleviating sensory complications. OBJECTIVE: We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which induces neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from glass catfish and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. METHODS: A rat model of forepaw denervation was used. rTMS was delivered every other day for 30 days, starting at the acute or at the chronic post-injury phase. A minimally-invasive neuromodulation via EPG was performed every day for 30 days starting at the chronic phase. A battery of behavioral tests was performed in the days and weeks following limb denervation in EPG-treated rats, and behavioral tests, fMRI and immunochemistry were performed in rTMS-treated rats. RESULTS: The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The results identify that both acute and delayed rTMS intervention facilitated rehabilitation. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. CONCLUSION: Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.
Authors: Juan Aguilar; Desiré Humanes-Valera; Elena Alonso-Calviño; Josué G Yague; Karen A Moxon; Antonio Oliviero; Guglielmo Foffani Journal: J Neurosci Date: 2010-06-02 Impact factor: 6.167
Authors: Ryan D Hunt; Ryan C Ashbaugh; Mark Reimers; Lalita Udpa; Gabriela Saldana De Jimenez; Michael Moore; Assaf A Gilad; Galit Pelled Journal: PLoS One Date: 2021-03-05 Impact factor: 3.240
Authors: Alesa H Netzley; Ryan D Hunt; Josue Franco-Arellano; Nicole Arnold; Ana I Vazquez; Kirk A Munoz; Aimee C Colbath; Tamara Reid Bush; Galit Pelled Journal: Sci Rep Date: 2021-11-22 Impact factor: 4.379