Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury
Immunization with neural derived peptides (INDP), as well as scar removal (SR) and the use of matrices with bone marrow-mesenchymal stem cells (MSCs), have been studied separately and proven to induce a functional and morphological improvement after spinal cord injury (SCI). Herein, we evaluated the...
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Frontiers Media S.A.
2020-04-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2020.00189/full |
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author | Roxana Rodríguez-Barrera Roxana Rodríguez-Barrera Adrián Flores-Romero Adrián Flores-Romero Vinnitsa Buzoianu-Anguiano Elisa Garcia Elisa Garcia Karla Soria-Zavala Karla Soria-Zavala Diego Incontri-Abraham Marcela Garibay-López Juan José Juárez-Vignon Whaley Antonio Ibarra Antonio Ibarra |
author_facet | Roxana Rodríguez-Barrera Roxana Rodríguez-Barrera Adrián Flores-Romero Adrián Flores-Romero Vinnitsa Buzoianu-Anguiano Elisa Garcia Elisa Garcia Karla Soria-Zavala Karla Soria-Zavala Diego Incontri-Abraham Marcela Garibay-López Juan José Juárez-Vignon Whaley Antonio Ibarra Antonio Ibarra |
author_sort | Roxana Rodríguez-Barrera |
collection | DOAJ |
description | Immunization with neural derived peptides (INDP), as well as scar removal (SR) and the use of matrices with bone marrow-mesenchymal stem cells (MSCs), have been studied separately and proven to induce a functional and morphological improvement after spinal cord injury (SCI). Herein, we evaluated the therapeutic effects of INDP combined with SR and a fibrin glue matrix (FGM) with MSCs (FGM-MSCs), on motor recovery, axonal regeneration-associated molecules and cytokine expression, axonal regeneration (catecholaminergic and serotonergic fibers), and the induction of neurogenesis after a chronic SCI. For this purpose, female adult Sprague-Dawley rats were subjected to SCI, 60 days after lesion, rats were randomly distributed in four groups: (1) Rats immunized with complete Freund's adjuvant + PBS (vehicle; PBS-I); (2) Rats with SR+ FGM-MSCs; (3) Rats with SR+ INDP + FGM-MSCs; (4) Rats only with INDP. Afterwards, we evaluated motor recovery using the BBB locomotor test. Sixty days after the therapy, protein expression of TNFα, IL-4, IL-10, BDNF, and GAP-43 were evaluated using ELISA assay. The number of catecholaminergic and serotonergic fibers were also determined. Neurogenesis was evaluated through immunofluorescence. The results show that treatment with INDP alone significantly increased motor recovery, anti-inflammatory cytokines, regeneration-associated molecules, axonal regeneration, and neurogenesis when compared to the rest of the groups. Our findings suggest that the combination therapy (SR + INDP + FGM-MSCs) modifies the non-permissive microenvironment post SCI, but it is not capable of inducing an appropriate axonal regeneration or neurogenesis when compared to the treatment with INDP alone. |
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spelling | doaj.art-8630eef6ecaa4b71853894b54c3314b32022-12-21T18:34:11ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-04-011110.3389/fneur.2020.00189516102Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord InjuryRoxana Rodríguez-Barrera0Roxana Rodríguez-Barrera1Adrián Flores-Romero2Adrián Flores-Romero3Vinnitsa Buzoianu-Anguiano4Elisa Garcia5Elisa Garcia6Karla Soria-Zavala7Karla Soria-Zavala8Diego Incontri-Abraham9Marcela Garibay-López10Juan José Juárez-Vignon Whaley11Antonio Ibarra12Antonio Ibarra13Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoProyecto CAMINA A.C., Mexico City, MexicoCentro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoProyecto CAMINA A.C., Mexico City, MexicoUIMEN, CMN Siglo XXI, Mexico City, MexicoCentro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoProyecto CAMINA A.C., Mexico City, MexicoCentro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoProyecto CAMINA A.C., Mexico City, MexicoCentro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoCentro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoCentro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoCentro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, MexicoProyecto CAMINA A.C., Mexico City, MexicoImmunization with neural derived peptides (INDP), as well as scar removal (SR) and the use of matrices with bone marrow-mesenchymal stem cells (MSCs), have been studied separately and proven to induce a functional and morphological improvement after spinal cord injury (SCI). Herein, we evaluated the therapeutic effects of INDP combined with SR and a fibrin glue matrix (FGM) with MSCs (FGM-MSCs), on motor recovery, axonal regeneration-associated molecules and cytokine expression, axonal regeneration (catecholaminergic and serotonergic fibers), and the induction of neurogenesis after a chronic SCI. For this purpose, female adult Sprague-Dawley rats were subjected to SCI, 60 days after lesion, rats were randomly distributed in four groups: (1) Rats immunized with complete Freund's adjuvant + PBS (vehicle; PBS-I); (2) Rats with SR+ FGM-MSCs; (3) Rats with SR+ INDP + FGM-MSCs; (4) Rats only with INDP. Afterwards, we evaluated motor recovery using the BBB locomotor test. Sixty days after the therapy, protein expression of TNFα, IL-4, IL-10, BDNF, and GAP-43 were evaluated using ELISA assay. The number of catecholaminergic and serotonergic fibers were also determined. Neurogenesis was evaluated through immunofluorescence. The results show that treatment with INDP alone significantly increased motor recovery, anti-inflammatory cytokines, regeneration-associated molecules, axonal regeneration, and neurogenesis when compared to the rest of the groups. Our findings suggest that the combination therapy (SR + INDP + FGM-MSCs) modifies the non-permissive microenvironment post SCI, but it is not capable of inducing an appropriate axonal regeneration or neurogenesis when compared to the treatment with INDP alone.https://www.frontiersin.org/article/10.3389/fneur.2020.00189/fullSCIImmunomodulationMSCFibrin tissue adhesiveA91 peptide |
spellingShingle | Roxana Rodríguez-Barrera Roxana Rodríguez-Barrera Adrián Flores-Romero Adrián Flores-Romero Vinnitsa Buzoianu-Anguiano Elisa Garcia Elisa Garcia Karla Soria-Zavala Karla Soria-Zavala Diego Incontri-Abraham Marcela Garibay-López Juan José Juárez-Vignon Whaley Antonio Ibarra Antonio Ibarra Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury Frontiers in Neurology SCI Immunomodulation MSC Fibrin tissue adhesive A91 peptide |
title | Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury |
title_full | Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury |
title_fullStr | Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury |
title_full_unstemmed | Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury |
title_short | Use of a Combination Strategy to Improve Morphological and Functional Recovery in Rats With Chronic Spinal Cord Injury |
title_sort | use of a combination strategy to improve morphological and functional recovery in rats with chronic spinal cord injury |
topic | SCI Immunomodulation MSC Fibrin tissue adhesive A91 peptide |
url | https://www.frontiersin.org/article/10.3389/fneur.2020.00189/full |
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