Journal
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
Volume 18, Issue 1, Pages 52-62Publisher
BENTHAM SCIENCE PUBL
DOI: 10.2174/1871527317666181105101756
Keywords
Evoked potentials; Fibrin glue; GAP43; mesenchymal stem cells; neural-derived peptides; protective autoimmunity; neural regeneration; scar removal; serotonin
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Funding
- National Council of Science and Technology of Mexico (CONACYT) [178544]
- Universidad Anahuac Mexico
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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 Dawlcy 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.
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