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CNS & Neurological Disorders - Drug Targets

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

DOI: 10.2174/1871527317666181105101756

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

Page: [52 - 62] Pages: 11

  • * (Excluding Mailing and Handling)

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.

Graphical Abstract

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