Hugh H Chan1, Connor A Wathen2, Nicole D Mathews1, Olivia Hogue3, James P Modic1, Ronak Kundalia1, Cara Wyant1, Hyun-Joo Park2, Imad M Najm4, Bruce D Trapp1, Andre G Machado5, Kenneth B Baker6. 1. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 2. Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA. 3. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA. 4. Epilepsy Center, Cleveland Clinic, Cleveland, OH, USA. 5. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA. 6. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA. Electronic address: Bakerk6@ccf.org.
Abstract
BACKGROUND: Many traumatic brain injury (TBI) survivors live with persistent disability from chronic motor deficits despite contemporary rehabilitation services, underscoring the need for novel treatment. OBJECTIVE/HYPOTHESIS: We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) can enhance post-stroke motor recovery and increase the expression of markers of long-term potentiation in perilesional cerebral cortex. We hypothesize that a similar beneficial effect will be for motor deficits induced by unilateral fluid percussion injury (FPI) in rodents through long-term potentiation- and anti-inflammatory based mechanisms. METHODS: Male Long Evans rats with a DBS macroelectrode in the LCN underwent FPI over contralateral primary motor cortex. After 4 weeks of spontaneous recovery, DBS treatment was applied for 4 weeks, with the pasta matrix, cylinder, and horizontal ladder tests used to evaluate motor performance. All animals were euthanized and tissue harvested for further analysis by histology, immunohistochemistry, RNA microarray assay and Western Blot. RESULTS: LCN DBS-treated animals experienced a significantly greater rate of motor recovery than untreated surgical controls, with treated animals showing enhanced expression of RNA and protein for excitability related genes, suppressed expression of pro-inflammatory genes, suppressed microglial and astrocytic activation, but proliferation of c-fos positive cells. Finally, our data suggest a possible role for anti-apoptotic effects with LCN DBS. CONCLUSION: LCN DBS enhanced the motor recovery following TBI, possibly by elevating the neuronal excitability at the perilesional area and mediating anti-apoptotic and anti-inflammatory effects.
BACKGROUND: Many traumatic brain injury (TBI) survivors live with persistent disability from chronic motor deficits despite contemporary rehabilitation services, underscoring the need for novel treatment. OBJECTIVE/HYPOTHESIS: We have previously shown that deep brain stimulation (DBS) of the lateral cerebellar nucleus (LCN) can enhance post-stroke motor recovery and increase the expression of markers of long-term potentiation in perilesional cerebral cortex. We hypothesize that a similar beneficial effect will be for motor deficits induced by unilateral fluid percussion injury (FPI) in rodents through long-term potentiation- and anti-inflammatory based mechanisms. METHODS: Male Long Evans rats with a DBS macroelectrode in the LCN underwent FPI over contralateral primary motor cortex. After 4 weeks of spontaneous recovery, DBS treatment was applied for 4 weeks, with the pasta matrix, cylinder, and horizontal ladder tests used to evaluate motor performance. All animals were euthanized and tissue harvested for further analysis by histology, immunohistochemistry, RNA microarray assay and Western Blot. RESULTS: LCN DBS-treated animals experienced a significantly greater rate of motor recovery than untreated surgical controls, with treated animals showing enhanced expression of RNA and protein for excitability related genes, suppressed expression of pro-inflammatory genes, suppressed microglial and astrocytic activation, but proliferation of c-fos positive cells. Finally, our data suggest a possible role for anti-apoptotic effects with LCN DBS. CONCLUSION: LCN DBS enhanced the motor recovery following TBI, possibly by elevating the neuronal excitability at the perilesional area and mediating anti-apoptotic and anti-inflammatory effects.
Authors: Sergiy Chornyy; Aniruddha Das; Julie A Borovicka; Davina Patel; Hugh H Chan; John K Hermann; Thomas C Jaramillo; Andre G Machado; Kenneth B Baker; Hod Dana Journal: Biomed Opt Express Date: 2021-07-16 Impact factor: 3.732