Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury

The regenerative capability of the central nervous system is limited after traumatic spinal cord injury (SCI) due to intrinsic and extrinsic factors that inhibit spinal cord regeneration, resulting in deficient functional recovery. It has been shown that strategies, such as pre-degenerated periphera...

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Main Authors: Vinnitsa Buzoianu-Anguiano, Jared Rivera-Osorio, Sandra Orozco-Suárez, Angélica Vega-García, Elisa García-Vences, Stephanie Sánchez-Torres, Ismael Jiménez-Estrada, Gabriel Guizar-Sahagún, Jose Mondragon-Caso, Francisca Fernández-Valverde, Ignacio Madrazo, Israel Grijalva
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-03-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fneur.2020.00136/full
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author Vinnitsa Buzoianu-Anguiano
Jared Rivera-Osorio
Sandra Orozco-Suárez
Angélica Vega-García
Elisa García-Vences
Stephanie Sánchez-Torres
Ismael Jiménez-Estrada
Gabriel Guizar-Sahagún
Gabriel Guizar-Sahagún
Jose Mondragon-Caso
Francisca Fernández-Valverde
Ignacio Madrazo
Israel Grijalva
author_facet Vinnitsa Buzoianu-Anguiano
Jared Rivera-Osorio
Sandra Orozco-Suárez
Angélica Vega-García
Elisa García-Vences
Stephanie Sánchez-Torres
Ismael Jiménez-Estrada
Gabriel Guizar-Sahagún
Gabriel Guizar-Sahagún
Jose Mondragon-Caso
Francisca Fernández-Valverde
Ignacio Madrazo
Israel Grijalva
author_sort Vinnitsa Buzoianu-Anguiano
collection DOAJ
description The regenerative capability of the central nervous system is limited after traumatic spinal cord injury (SCI) due to intrinsic and extrinsic factors that inhibit spinal cord regeneration, resulting in deficient functional recovery. It has been shown that strategies, such as pre-degenerated peripheral nerve (PPN) grafts or the use of bone marrow stromal cells (BMSCs) or exogenous molecules, such as chondroitinase ABC (ChABC) promote axonal growth and remyelination, resulting in an improvement in locomotor function. These treatments have been primarily assessed in acute injury models. The aim of the present study is to evaluate the ability of several single and combined treatments in order to modify the course of chronic complete SCI in rats. A complete cord transection was performed at the T9 level. One month later, animals were divided into five groups: original injury only (control group), and original injury plus spinal cord re-transection to create a gap to accommodate BMSCs, PPN, PPN + BMSCs, and PPN + BMSCs + ChABC. In comparison with control and single-treatment groups (PPN and BMSCs), combined treatment groups (PPN + BMSCs and PPN + BMSCs + ChABC) showed significative axonal regrowth, as revealed by an increase in GAP-43 and MAP-1B expression in axonal fibers, which correlated with an improvement in locomotor function. In conclusion, the combined therapies tested here improve locomotor function by enhancing axonal regeneration in rats with chronic SCI. Further studies are warranted to refine this promising line of research for clinical purposes.
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spelling doaj.art-0a1415c5c75747c7a5dba36e56c4e5852022-12-22T03:05:49ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-03-011110.3389/fneur.2020.00136516292Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord InjuryVinnitsa Buzoianu-Anguiano0Jared Rivera-Osorio1Sandra Orozco-Suárez2Angélica Vega-García3Elisa García-Vences4Stephanie Sánchez-Torres5Ismael Jiménez-Estrada6Gabriel Guizar-Sahagún7Gabriel Guizar-Sahagún8Jose Mondragon-Caso9Francisca Fernández-Valverde10Ignacio Madrazo11Israel Grijalva12Hospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoHospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoHospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoHospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoCentro de Investigación en Ciencias de la Salud, Universidad Anahuac México Campus Norte, Mexico City, MexicoHospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, CINVESTAV, IPN, Mexico City, MexicoHospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoDepartamento de Cirugía Experimental, Proyecto Camina AC, Mexico City, MexicoCentro de Investigación en Ciencias de la Salud, Universidad Anahuac México Campus Norte, Mexico City, MexicoLaboratorio de Patología Experimental, Instituto Nacional de Neurología y Neurocirugía, Mexico City, MexicoHospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoHospital de Especialidades CMN Siglo XXI IMSS, Unidad de Investigación Médica en Enfermedades Neurologicas, Mexico City, MexicoThe regenerative capability of the central nervous system is limited after traumatic spinal cord injury (SCI) due to intrinsic and extrinsic factors that inhibit spinal cord regeneration, resulting in deficient functional recovery. It has been shown that strategies, such as pre-degenerated peripheral nerve (PPN) grafts or the use of bone marrow stromal cells (BMSCs) or exogenous molecules, such as chondroitinase ABC (ChABC) promote axonal growth and remyelination, resulting in an improvement in locomotor function. These treatments have been primarily assessed in acute injury models. The aim of the present study is to evaluate the ability of several single and combined treatments in order to modify the course of chronic complete SCI in rats. A complete cord transection was performed at the T9 level. One month later, animals were divided into five groups: original injury only (control group), and original injury plus spinal cord re-transection to create a gap to accommodate BMSCs, PPN, PPN + BMSCs, and PPN + BMSCs + ChABC. In comparison with control and single-treatment groups (PPN and BMSCs), combined treatment groups (PPN + BMSCs and PPN + BMSCs + ChABC) showed significative axonal regrowth, as revealed by an increase in GAP-43 and MAP-1B expression in axonal fibers, which correlated with an improvement in locomotor function. In conclusion, the combined therapies tested here improve locomotor function by enhancing axonal regeneration in rats with chronic SCI. Further studies are warranted to refine this promising line of research for clinical purposes.https://www.frontiersin.org/article/10.3389/fneur.2020.00136/fullaxonal regenerationbone marrow stromal cell transplantpre-degeneration peripheral nerve transplantBBB modified scorekinematic analysisfunctional recovery
spellingShingle Vinnitsa Buzoianu-Anguiano
Jared Rivera-Osorio
Sandra Orozco-Suárez
Angélica Vega-García
Elisa García-Vences
Stephanie Sánchez-Torres
Ismael Jiménez-Estrada
Gabriel Guizar-Sahagún
Gabriel Guizar-Sahagún
Jose Mondragon-Caso
Francisca Fernández-Valverde
Ignacio Madrazo
Israel Grijalva
Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury
Frontiers in Neurology
axonal regeneration
bone marrow stromal cell transplant
pre-degeneration peripheral nerve transplant
BBB modified score
kinematic analysis
functional recovery
title Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury
title_full Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury
title_fullStr Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury
title_full_unstemmed Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury
title_short Single vs. Combined Therapeutic Approaches in Rats With Chronic Spinal Cord Injury
title_sort single vs combined therapeutic approaches in rats with chronic spinal cord injury
topic axonal regeneration
bone marrow stromal cell transplant
pre-degeneration peripheral nerve transplant
BBB modified score
kinematic analysis
functional recovery
url https://www.frontiersin.org/article/10.3389/fneur.2020.00136/full
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