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- Title
Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury.
- Authors
Martiñón, Susana; García-Vences, Elisa; Toscano-Tejeida, Diana; Flores-Romero, Adrian; Rodriguez-Barrera, Roxana; Ferrusquia, Manuel; Hernández-Muñoz, Rolando E.; Ibarra, Antonio
- Abstract
<bold>Background: </bold>After spinal cord (SC)-injury, a non-modulated immune response contributes to the damage of neural tissue. Protective autoimmunity (PA) is a T cell mediated, neuroprotective response induced after SC-injury. Immunization with neural-derived peptides (INDP), such as A91, has shown to promote-in vitro-the production of neurotrophic factors. However, the production of these molecules has not been studied at the site of injury.<bold>Results: </bold>In order to evaluate these issues, we performed four experiments in adult female Sprague-Dawley rats. In the first one, brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) concentrations were evaluated at the site of lesion 21 days after SC-injury. BDNF and NT-3 were significantly increased in INDP-treated animals. In the second experiment, proliferation of anti-A91 T cells was assessed at chronic stages of injury. In this case, we found a significant proliferation of these cells in animals subjected to SC-injury + INDP. In the third experiment, we explored the amount of BDNF and NT3 at the site of injury in the chronic phase of rats subjected to either SC-contusion (SCC; moderate or severe) or SC-transection (SCT; complete or incomplete). The animals were treated with INDP immediately after injury. Rats subjected to moderate contusion or incomplete SCT showed significantly higher levels of BDNF and NT-3 as compared to PBS-immunized ones. In rats with severe SCC and complete SCT, BDNF and NT-3 concentrations were barely detected. Finally, in the fourth experiment we assessed motor function recovery in INDP-treated rats with moderate SC-injury. Rats immunized with A91 showed a significantly higher motor recovery from the first week and up to 4 months after SC-injury.<bold>Conclusions: </bold>The results of this study suggest that PA boosted by immunization with A91 after moderate SC-injury can exert its benefits even at chronic stages, as shown by long-term production of BDNF and NT-3 and a substantial improvement in motor recovery.
- Subjects
BRAIN-derived neurotrophic factor; IMMUNIZATION; T cells; PROMOTERS (Genetics); NEUROTROPHINS; ANIMAL experimentation; BIOLOGICAL models; CHRONIC diseases; CONVALESCENCE; IMMUNITY; MOTOR ability; NERVE tissue proteins; PEPTIDES; RATS; STATISTICAL sampling; SPINAL cord; SPINAL cord injuries; TIME; SEVERITY of illness index; THERAPEUTICS
- Publication
BMC Neuroscience, 2016, Vol 17, p1
- ISSN
1471-2202
- Publication type
journal article
- DOI
10.1186/s12868-016-0267-6