Samuel S Shin1, Vijai Krishnan2, William Stokes3, Courtney Robertson4, Pablo Celnik5, Yanrong Chen3, Xiaolei Song3, Hanzhang Lu3, Peiying Liu3, Galit Pelled6. 1. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 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. 3. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4. Department of Anesthesiology/Critical Care Medicine and Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Physical Medicine and Rehabilitation, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 6. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 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@egr.msu.edu.
Abstract
BACKGROUND: Therapeutic strategies for traumatic brain injury (TBI) in the last three decades have failed to show significant benefit in large scale studies. Given the multitude of pathological mechanisms involved in TBI, strategies focusing on multimodality regimen have gained interest as promising future interventions. HYPOTHESIS: We hypothesized that combining noninvasive transcranial magnetic stimulation (TMS) with rehabilitative training in an environmental enrichment (EE) can facilitate post-TBI recovery in rats via cortical excitability and reorganization. METHODS: We subjected rats to controlled cortical impact, and then assigned them to one of four groups: 1. No treatments (TBI), 2. EE after injury (TBI + EE), 3. TMS for one week (TBI + TMS), and 4. TMS for one week combined with EE (TBI + TMS/EE). For TMS, a 10 Hz repetitive TMS protocol was used. RESULTS: At 7 days, TBI + TMS and TBI + TMS/EE groups had significantly increased primary somatosensory cortex local field potential (LFP) compared to TBI and TBI + EE groups (P < 0.05). Also, TBI + TMS/EE group had significantly improved performance on beam walk test compared to TBI group (P < 0.005). At 6 weeks, there was significantly higher response in TBI + TMS/EE group compared to TBI + TMS for somatosensory cortex LFP (P < 0.05), bicep motor evoked potentials (MEP) (P < 0.05), challenge ladder test performance (P < 0.01), and fMRI responses to tactile forepaw stimulation. CONCLUSIONS: We demonstrate here for the first time the mechanism by which combined therapy using TMS and EE after TBI leads to functional improvement, possibly via cortical excitability and reorganization.
BACKGROUND: Therapeutic strategies for traumatic brain injury (TBI) in the last three decades have failed to show significant benefit in large scale studies. Given the multitude of pathological mechanisms involved in TBI, strategies focusing on multimodality regimen have gained interest as promising future interventions. HYPOTHESIS: We hypothesized that combining noninvasive transcranial magnetic stimulation (TMS) with rehabilitative training in an environmental enrichment (EE) can facilitate post-TBI recovery in rats via cortical excitability and reorganization. METHODS: We subjected rats to controlled cortical impact, and then assigned them to one of four groups: 1. No treatments (TBI), 2. EE after injury (TBI + EE), 3. TMS for one week (TBI + TMS), and 4. TMS for one week combined with EE (TBI + TMS/EE). For TMS, a 10 Hz repetitive TMS protocol was used. RESULTS: At 7 days, TBI + TMS and TBI + TMS/EE groups had significantly increased primary somatosensory cortex local field potential (LFP) compared to TBI and TBI + EE groups (P < 0.05). Also, TBI + TMS/EE group had significantly improved performance on beam walk test compared to TBI group (P < 0.005). At 6 weeks, there was significantly higher response in TBI + TMS/EE group compared to TBI + TMS for somatosensory cortex LFP (P < 0.05), bicep motor evoked potentials (MEP) (P < 0.05), challenge ladder test performance (P < 0.01), and fMRI responses to tactile forepaw stimulation. CONCLUSIONS: We demonstrate here for the first time the mechanism by which combined therapy using TMS and EE after TBI leads to functional improvement, possibly via cortical excitability and reorganization.
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