title: Immunization with neural derived peptides plus scar removal induces a permissive microenvironment, and improves locomotor recovery after chronic spinal cord injury.
abstract: Immunization with neural derived peptides (INDP) as well as scar removal-separately-have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated and cytokine gene expression, and axonal regeneration after chronic SCI. Scar removal was conducted through a single incision with a double-bladed scalpel along the stump, and scar renewal was halted by adding α,α'-dipyridyl.
  
  
  
  During the chronic injury stage, two experiments were undertaken. The first experiment was aimed at testing the therapeutic effect of INDP combined with scar removal. Sixty days after therapeutic intervention, the expression of genes encoding for TNFα, IFNγ, IL4, TGFβ, BDNF, IGF1, and GAP43 was evaluated at the site of injury. Tyrosine hydroxylase and 5-hydroxytryptamine positive fibers were also studied. Locomotor evaluations showed a significant recovery in the group treated with scar removal + INDP. Moreover; this group presented a significant increase in IL4, TGFβ, BDNF, IGF1, and GAP43 expression, but a decrease of TNFα and IFNγ. Also, the spinal cord of animals receiving both treatments presented a significant increase of serotonergic and catecholaminergic fibers as compared to other the groups. The second experiment compared the results of the combined approach versus INDP alone. Rats receiving INDP likewise showed improved motor recovery, although on a lesser scale than those who received the combined treatment. An increase in inflammation and regeneration-associated gene expression, as well as in the percentage of serotonergic and catecholaminergic fibers was observed in INDP-treated rats to a lesser degree than those in the combined therapy group.
  
  
  
  These findings suggest that INDP, both alone and in combination with scar removal, could modify the non-permissive microenvironment prevailing at the chronic phase of SCI, providing the opportunity of improving motor recovery.
authors.affiliation: Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Centro de Investigación del Proyecto CAMINA A.C., Ciudad de México, Mexico.|Posgrado en Biología Experimental, UAMI, Ciudad de México, Mexico.
authors.forename: Roxana
authors.initials: R
authors.lastname: Rodríguez-Barrera
authors.affiliation: Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Centro de Investigación del Proyecto CAMINA A.C., Ciudad de México, Mexico.
authors.forename: Adrián
authors.initials: A
authors.lastname: Flores-Romero
authors.affiliation: Facultad de Medicina, UNAM, Ciudad de México, Mexico.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Fernández-Presas
authors.affiliation: Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Centro de Investigación del Proyecto CAMINA A.C., Ciudad de México, Mexico.
authors.forename: Elisa
authors.initials: E
authors.lastname: García-Vences
authors.affiliation: Hospital de Pediatría CMN Siglo XXI, Ciudad de México, Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Silva-García
authors.affiliation: Lab. Bioenergética y Envejecimiento Celular, UAMI, Ciudad de México, Mexico.
authors.forename: Mina
authors.initials: M
authors.lastname: Konigsberg
authors.affiliation: Centro de Investigación del Proyecto CAMINA A.C., Ciudad de México, Mexico.|Hospital de Pediatría CMN Siglo XXI, Ciudad de México, Mexico.
authors.forename: Liliana
authors.initials: L
authors.lastname: Blancas-Espinoza
authors.affiliation: UIMEN, CMN Siglo XXI, Ciudad de México, Mexico.
authors.forename: Vinnitsa
authors.initials: V
authors.lastname: Buzoianu-Anguiano
authors.affiliation: Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Centro de Investigación del Proyecto CAMINA A.C., Ciudad de México, Mexico.
authors.forename: Karla
authors.initials: K
authors.lastname: Soria-Zavala
authors.affiliation: Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.|Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico.
authors.forename: Paola
authors.initials: P
authors.lastname: Suárez-Meade
authors.affiliation: Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico. jose.ibarra@anahuac.mx.|Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan, Estado de México, Mexico. jose.ibarra@anahuac.mx.|Centro de Investigación del Proyecto CAMINA A.C., Ciudad de México, Mexico. jose.ibarra@anahuac.mx.
authors.forename: Antonio
authors.identifier: 0000-0003-2489-4689
authors.initials: A
authors.lastname: Ibarra
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002908:Chronic Disease; D002921:Cicatrix / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects*; D009479:Neuropeptides / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D058630:Spinal Cord Regeneration / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D019922:GAP-43 Protein; D009479:Neuropeptides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma
keywords: A91; Immunomodulation; Neural antigens; Paraplegia; Protective autoimmunity; Regeneration