n-(2-naphthalene)sulfonyl-dl-tryptophan and Spinal-Cord-Injuries

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.

Topics: 2,2'-Dipyridyl; Animals; Cicatrix; Combined Modality Therapy; Evoked Potentials; Female; Freund's Adjuvant; Gene Expression; Mesenchymal Stem Cell Transplantation; Motor Activity; Nerve Regeneration; Rats; Recovery of Function; Spinal Cord Injuries; Tryptophan

Immune system activity has traditionally been considered harmful for recovery after spinal cord injury (SCI). Recent evidence suggests, however, that immune activity--and specifically autoimmune activity--is evoked by the insult, is beneficial if properly regulated and is amenable to boosting. Thus, for example, vaccination with an altered peptide ligand derived from myelin basic protein reduces the progressive degeneration of neurons that escaped the initial insult, thereby promoting recovery after SCI. As the steroid drug methylprednisolone (MP) is currently the only treatment available for patients with SCI, our purpose in the present study was to examine the mutual compatibility of the two treatments within the post-traumatic therapeutic window. We show, using rats of two different strains, that if MP is injected concomitantly with the therapeutic vaccination, the beneficial effect of the vaccination is diminished. However, if MP is given immediately after the insult and the vaccination 48 h later, MP does not detract from the beneficial effect of the vaccination. These results demonstrate that the therapeutic window after SCI can accommodate immediate administration of MP plus a delayed therapeutic vaccination.

Topics: Analysis of Variance; Animals; Behavior, Animal; Cell Count; Cell Division; Cells, Cultured; Dextrans; Ectodysplasins; Encephalomyelitis, Autoimmune, Experimental; Female; Immunohistochemistry; Immunotherapy, Active; Laminectomy; Membrane Proteins; Methylprednisolone; Motor Activity; Mycobacterium; Myelin Basic Protein; Neuroprotective Agents; Peptide Fragments; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Rhodamines; Species Specificity; Spinal Cord Injuries; T-Lymphocytes; Time Factors; Tryptophan