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Motor Recovery after Chronic Spinal Cord Transection in Rats: A Proof-of-Concept Study Evaluating a Combined Strategy

[ Vol. 18 , Issue. 1 ]

Author(s):

Antonio Ibarra*, Erika Mendieta-Arbesú, Paola Suarez-Meade, Elisa García-Vences, Susana Martiñón, Roxana Rodriguez-Barrera, Joel Lomelí, Adrian Flores-Romero, Raúl Silva-García, Vinnitsa Buzoianu-Anguiano, Cesar V. Borlongan and Tamara D. Frydman   Pages 52 - 62 ( 11 )

Abstract:


Background: The chronic phase of Spinal Cord (SC) injury is characterized by the presence of a hostile microenvironment that causes low activity and a progressive decline in neurological function; this phase is non-compatible with regeneration. Several treatment strategies have been investigated in chronic SC injury with no satisfactory results. OBJECTIVE- In this proof-of-concept study, we designed a combination therapy (Comb Tx) consisting of surgical glial scar removal plus scar inhibition, accompanied with implantation of mesenchymal stem cells (MSC), and immunization with neural-derived peptides (INDP).

Methods: This study was divided into three subsets, all in which Sprague Dawley rats were subjected to a complete SC transection. Sixty days after injury, animals were randomly allocated into two groups for therapeutic intervention: control group and animals receiving the Comb-Tx. Sixty-three days after treatment we carried out experiments analyzing motor recovery, presence of somatosensory evoked potentials, neural regeneration-related genes, and histological evaluation of serotoninergic fibers.

Results: Comb-Tx induced a significant locomotor and electrophysiological recovery. An increase in the expression of regeneration-associated genes and the percentage of 5-HT+ fibers was noted at the caudal stump of the SC of animals receiving the Comb-Tx. There was a significant correlation of locomotor recovery with positive electrophysiological activity, expression of GAP43, and percentage of 5-HT+ fibers.

Conclusion: Comb-Tx promotes motor and electrophysiological recovery in the chronic phase of SC injury subsequent to a complete transection. Likewise, it is capable of inducing the permissive microenvironment to promote axonal regeneration.

Keywords:

Evoked potentials, Fibrin glue, GAP43, mesenchymal stem cells, neural-derived peptides, protective autoimmunity, neural regeneration, scar removal, serotonin.

Affiliation:

Centro de Investigacion en Ciencias de la Salud (CICSA), Universidad Anahuac Mexico Campus Norte, Huixquilucan Estado de Mexico, Centro de Investigacion en Ciencias de la Salud (CICSA), Universidad Anahuac Mexico Campus Norte, Huixquilucan Estado de Mexico, Centro de Investigacion en Ciencias de la Salud (CICSA), Universidad Anahuac Mexico Campus Norte, Huixquilucan Estado de Mexico, Centro de Investigacion en Ciencias de la Salud (CICSA), Universidad Anahuac Mexico Campus Norte, Huixquilucan Estado de Mexico, Instituto Nacional de Psiquiatria "Ramon de la Fuente Muniz", Ciudad de Mexico, Centro de Investigacion en Ciencias de la Salud (CICSA), Universidad Anahuac Mexico Campus Norte, Huixquilucan Estado de Mexico, Instituto Politecnico Nacional, Escuela Superior de Medicina, Ciudad de Mexico, Centro de Investigacion en Ciencias de la Salud (CICSA), Universidad Anahuac Mexico Campus Norte, Huixquilucan Estado de Mexico, Hospital de Pediatria, CMN Siglo XXI, Ciudad de Mexico, UIMEN, CMN Siglo XXI, Ciudad de Mexico, Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL 33612, Centro de Investigacion en Ciencias de la Salud (CICSA), Universidad Anahuac Mexico Campus Norte, Huixquilucan Estado de Mexico

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