Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (7): 1273-1280.doi: 10.4103/1673-5374.301485

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Neuroprotective effect of immunomodulatory peptides in rats with traumatic spinal cord injury

Dulce Parra-Villamar1, Liliana Blancas-Espinoza1, Elisa Garcia-Vences2, 3, Juan Herrera-García1, Adrian Flores-Romero2, 3, Alberto Toscano-Zapien1, Jonathan Vilchis Villa1, Rodríguez Barrera-Roxana2, 3, Soria Zavala Karla1, 2, Antonio Ibarra2, 3, *, Raúl Silva-García1, *   

  1. 1 Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI; Instituto Mexicano del Seguro Social; Ciudad de México, México;  2 Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México, Campus Norte, Huixquilucan, Edo de México, México;  3 Centro de Investigación del Proyecto Camina A.C, Ciudad de México, México 
  • Online:2021-07-15 Published:2021-01-07
  • Contact: Antonio Ibarra, MD, MSc, DSc, jose.ibarra@anahuac.mx; Raúl Silva-García, MSc, DSc, silgarrul@yahoo.com.mx.
  • Supported by:
    This study was supported by Fondo de Investigación en Salud of the Instituto Mexicano del Seguro Social (IMSS), under the support No. FIS/IMSS/PROT/G17/1676 and FIS/IMSS/PROT/G18/1825 and the scholarship granted to the students of Master’s degree by Consejo Nacional de Ciencia y Tecnología (CONACYT) and IMSS.

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Abstract: Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury (SCI). Nevertheless, neither strategy has achieved a convincing effect. We purposed a combined therapy of immunomodulatory peptides that individually have shown significant effects on motor functional recovery in rats with SCI. The objective of this study was to investigate the effects of the combined therapy of monocyte locomotion inhibitor factor (MLIF), A91 peptide, and glutathione monoethyl ester (GSH-MEE) on chronic-stage spinal cord injury. Female Sprague-Dawley rats underwent a laminectomy of the T9 vertebra and a moderate contusion. Six groups were included: sham, PBS, MLIF + A91, MLIF + GSH-MEE, A91 + GSH-MEE, and MLIF + A91 + GSH-MEE. Two months after injury, motor functional recovery was evaluated using the open field test. Parenchyma and white matter preservation was evaluated using hematoxylin & eosin staining and Luxol Fast Blue staining, respectively. The number of motoneurons in the ventral horn and the number of axonal fibers were determined using hematoxylin & eosin staining and immunohistochemistry, respectively. Collagen deposition was evaluated using Masson’s trichrome staining. The combined therapy of MLIF, A91, and GSH-MEE greatly contributed to motor functional recovery and preservation of the medullary parenchyma, white matter, motoneurons, and axonal fibres, and reduced the deposition of collagen in the lesioned area. The combined therapy of MLIF, A91, and GSH-MEE preserved spinal cord tissue integrity and promoted motor functional recovery of rats after SCI. This study was approved by the National Commission for Scientific Research on Bioethics and Biosafety of the Instituto Mexicano del Seguro Social under registration number R-2015-785-116 (approval date November 30, 2015) and R-2017-3603-33 (approval date June 5, 2017). 

Key words: glutathione monoethyl ester, monocyte locomotion inhibitor factor, motor functional recovery, neuroprotection, neurorestoration, peptides, protective autoimmunity, spinal cord injury