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Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation

Although epidural spinal stimulation (ESS) results in promising therapeutic effects in individuals with spinal cord injury (SCI), its potential to generate functional motor recovery varies between individuals and remains largely unclear. However, both preclinical and clinical studies indicate the ca...

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Autores principales: Taccola, Giuliano, Salazar, Betsy Habeth, Apicella, Rosamaria, Hogan, Matthew Kevin, Horner, Philip John, Sayenko, Dimitry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372902/
https://www.ncbi.nlm.nih.gov/pubmed/32760254
http://dx.doi.org/10.3389/fnsys.2020.00044
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author Taccola, Giuliano
Salazar, Betsy Habeth
Apicella, Rosamaria
Hogan, Matthew Kevin
Horner, Philip John
Sayenko, Dimitry
author_facet Taccola, Giuliano
Salazar, Betsy Habeth
Apicella, Rosamaria
Hogan, Matthew Kevin
Horner, Philip John
Sayenko, Dimitry
author_sort Taccola, Giuliano
collection PubMed
description Although epidural spinal stimulation (ESS) results in promising therapeutic effects in individuals with spinal cord injury (SCI), its potential to generate functional motor recovery varies between individuals and remains largely unclear. However, both preclinical and clinical studies indicate the capacity of electrical and pharmacological interventions to synergistically increase the engagement of spinal sensorimotor networks and regain motor function after SCI. This study explored whether selective pharmacological antagonism of the adenosine A1 receptor subtype synergizes with ESS, thereby increasing motor response. We hypothesized that selective pharmacological antagonism of A1 receptors during ESS would produce facilitatory effects in spinal sensorimotor networks detected as an increased amplitude of spinally-evoked motor potentials and sustained duration of ESS induced activity. Terminal experiments were performed in adult rats using trains of stereotyped pulses at 40 Hz delivered at L5 with the local administration to the cord of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We demonstrated that ESS combined with the blockage of A1 receptors increased the magnitude of the endogenous modulation and postponed the decay of responses that occur during ESS alone. Although DPCPX significantly increased the yield of repetitive stimulation in intact spinal cords, the effects of A1 antagonism on motor evoked responses after an acute spinal transection was not detected. These studies support the future investigation of the optimal dosage, methods of delivery, and systemic effects of the synergistic application of A1 antagonists and spinal stimulation in the intact and injured spinal cord.
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spelling pubmed-73729022020-08-04 Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation Taccola, Giuliano Salazar, Betsy Habeth Apicella, Rosamaria Hogan, Matthew Kevin Horner, Philip John Sayenko, Dimitry Front Syst Neurosci Neuroscience Although epidural spinal stimulation (ESS) results in promising therapeutic effects in individuals with spinal cord injury (SCI), its potential to generate functional motor recovery varies between individuals and remains largely unclear. However, both preclinical and clinical studies indicate the capacity of electrical and pharmacological interventions to synergistically increase the engagement of spinal sensorimotor networks and regain motor function after SCI. This study explored whether selective pharmacological antagonism of the adenosine A1 receptor subtype synergizes with ESS, thereby increasing motor response. We hypothesized that selective pharmacological antagonism of A1 receptors during ESS would produce facilitatory effects in spinal sensorimotor networks detected as an increased amplitude of spinally-evoked motor potentials and sustained duration of ESS induced activity. Terminal experiments were performed in adult rats using trains of stereotyped pulses at 40 Hz delivered at L5 with the local administration to the cord of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We demonstrated that ESS combined with the blockage of A1 receptors increased the magnitude of the endogenous modulation and postponed the decay of responses that occur during ESS alone. Although DPCPX significantly increased the yield of repetitive stimulation in intact spinal cords, the effects of A1 antagonism on motor evoked responses after an acute spinal transection was not detected. These studies support the future investigation of the optimal dosage, methods of delivery, and systemic effects of the synergistic application of A1 antagonists and spinal stimulation in the intact and injured spinal cord. Frontiers Media S.A. 2020-07-14 /pmc/articles/PMC7372902/ /pubmed/32760254 http://dx.doi.org/10.3389/fnsys.2020.00044 Text en Copyright © 2020 Taccola, Salazar, Apicella, Hogan, Horner and Sayenko. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Taccola, Giuliano
Salazar, Betsy Habeth
Apicella, Rosamaria
Hogan, Matthew Kevin
Horner, Philip John
Sayenko, Dimitry
Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation
title Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation
title_full Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation
title_fullStr Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation
title_full_unstemmed Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation
title_short Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation
title_sort selective antagonism of a1 adenosinergic receptors strengthens the neuromodulation of the sensorimotor network during epidural spinal stimulation
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372902/
https://www.ncbi.nlm.nih.gov/pubmed/32760254
http://dx.doi.org/10.3389/fnsys.2020.00044
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