Motor Recovery after Chronic Spinal Cord Transection in Rats: A Proof-of-Concept Study Evaluating a Combined Strategy.
2,2'-Dipyridyl
/ therapeutic use
Animals
Cicatrix
/ surgery
Combined Modality Therapy
/ methods
Evoked Potentials
/ physiology
Female
Freund's Adjuvant
/ therapeutic use
Gene Expression
/ drug effects
Mesenchymal Stem Cell Transplantation
Motor Activity
/ drug effects
Nerve Regeneration
/ drug effects
Rats
Recovery of Function
/ drug effects
Spinal Cord Injuries
/ drug therapy
Tryptophan
/ analogs & derivatives
Evoked potentials
Fibrin glue
GAP43
mesenchymal stem cells
neural regeneration
neural-derived peptides
protective autoimmunity
scar removal
serotonin.
Journal
CNS & neurological disorders drug targets
ISSN: 1996-3181
Titre abrégé: CNS Neurol Disord Drug Targets
Pays: United Arab Emirates
ID NLM: 101269155
Informations de publication
Date de publication:
2019
2019
Historique:
received:
09
08
2018
revised:
20
10
2018
accepted:
29
10
2018
pubmed:
6
11
2018
medline:
17
3
2020
entrez:
6
11
2018
Statut:
ppublish
Résumé
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). 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 30394222
pii: CNSNDDT-EPUB-94256
doi: 10.2174/1871527317666181105101756
doi:
Substances chimiques
N-(2-naphthalene)sulfonyl-DL-tryptophan
40356-23-8
2,2'-Dipyridyl
551W113ZEP
Tryptophan
8DUH1N11BX
Freund's Adjuvant
9007-81-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
52-62Informations de copyright
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