Immunization with neural-derived antigens inhibits lipid peroxidation after spinal cord injury

Ibarra, Antonio; García, Elisa; Flores, Nayeli; Martiñón, S.; Reyes, R Martínez; Campos, Marı́a G.; Maciel, Marcial; Mestre, Humberto

doi:10.1016/j.neulet.2010.04.003

Cited by 39 publications

(60 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…According to the study reported by Beck et al [16], immune cells serve as a reparative factor in chronic stages of lesion since, the blockade of these, reduced motor recovery and myelination in the injured spinal cord. In acute SCI, the protective and restorative actions of immune cells have also been widely demonstrated [11,12,15]. The findings of the present manuscript confirm the presence of MBP-reactive elements which could be beneficial in promoting restorative processes in patients with chronic SCI.…”

Section: Discussionsupporting

confidence: 78%

“…This is due to the need of conclusive research that clarifies the exact role the immunological cells play after spinal cord trauma. At the moment, some studies suggest that immune cells contribute in expanding tissue damage after injury [8,9]; other findings provide significant evidence on the participation of immune cells in promoting neuroprotection and neuroregeneration [10][11][12]. Collectively, these findings provide interesting elements to hypothesize a conciliatory scenario where these autoreactive responses could behave as a harmful or beneficial phenomenon.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Autoreactivity against myelin basic protein in patients with chronic paraplegia

et al. 2011

Self Cite

View full text Add to dashboard Cite

Introduction Previous studies have shown the existence of either cellular or humoral MBP-reactive elements up to 5 years after spinal cord injury (SCI), but not the presence of both after 10 years. Materials and methods Twelve SCI patients, with more than 10 years of evolution, and 18 healthy blood donors were studied. Lymphocyte proliferation (colorimetricBrdU ELISA assay) and antibody titers against MBP (ELISA Human IgG MBP-specific assay) were assessed. Results SCI patients presented a significant T-cell proliferation against MBP (lymphocyte proliferation index: 3.7 ± 1.5, mean ± SD) compared to control individuals (0.7 ± 0.3; P \ 0.001). Humoral response analysis yielded a significant difference (P \ 0.0001) between the antibody titers of controls and SCI patients. A significant correlation between cellular and humoral responses was observed. Finally, patients with an ASIA B presented the highest immune responses. Conclusion This work demonstrates, for the first time, the existence of both cellular and humoral responses against MBP in the chronic stages ([10 years) of injury.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 98%

Autoreactivity against myelin basic protein in patients with chronic paraplegia

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nevertheless, there is strong evidence supporting that immune cells improve the neurological outcome after injury [6], [13]. For instance, the immune response developed after immunization with neural-derived peptides (PA) is capable of ameliorating neurotoxicity [14], [15], lipid peroxidation [16] and other degenerative mechanisms [7], [17], [18]. It is clear that immune cells promote a microenvironment where different destructive phenomena are being suppressed, providing tissue protection and improving the functional recovery [2].…”

Section: Discussionmentioning

confidence: 99%

Development of Protective Autoimmunity by Immunization with a Neural-Derived Peptide Is Ineffective in Severe Spinal Cord Injury

Martiñón¹,

García

Gutiérrez‐Ospina

et al. 2012

PLoS ONE

Self Cite

View full text Add to dashboard Cite

Protective autoimmunity (PA) is a physiological response to central nervous system trauma that has demonstrated to promote neuroprotection after spinal cord injury (SCI). To reach its beneficial effect, PA should be boosted by immunizing with neural constituents or neural-derived peptides such as A91. Immunizing with A91 has shown to promote neuroprotection after SCI and its use has proven to be feasible in a clinical setting. The broad applications of neural-derived peptides make it important to determine the main features of this anti-A91 response. For this purpose, adult Sprague-Dawley rats were subjected to a spinal cord contusion (SCC; moderate or severe) or a spinal cord transection (SCT; complete or incomplete). Immediately after injury, animals were immunized with PBS or A91. Motor recovery, T cell-specific response against A91 and the levels of IL-4, IFN-γ and brain-derived neurotrophic factor (BDNF) released by A91-specific T (TA91) cells were evaluated. Rats with moderate SCC, presented a better motor recovery after A91 immunization. Animals with moderate SCC or incomplete SCT showed significant T cell proliferation against A91 that was characterized chiefly by the predominant production of IL-4 and the release of BDNF. In contrast, immunization with A91 did not promote a better motor recovery in animals with severe SCC or complete SCT. In fact, T cell proliferation against A91 was diminished in these animals. The present results suggest that the effective development of PA and, consequently, the beneficial effects of immunizing with A91 significantly depend on the severity of SCI. This could mainly be attributed to the lack of TA91 cells which predominantly showed to have a Th2 phenotype capable of producing BDNF, further promoting neuroprotection.

show abstract

“…Activation of T-Lymphocytes by A91-peptide induces an anti-inflammatory Th2 response that allows microglia to differentiate into an M2 phenotype. The resulting microenvironment after immunization is characterized by a low production of free radicals and several neuroprotective mechanisms [7, 8]. The therapeutic effect of PA has already been reported when INDP is performed immediately after SCI; however, there is no published data describing the effect of this strategy when administered during the chronic phase of injury.…”

Section: Introductionmentioning

confidence: 99%

Immunization with neural derived peptides plus scar removal induces a permissive microenvironment, and improves locomotor recovery after chronic spinal cord injury

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundImmunization with neural derived peptides (INDP) as well as scar removal—separately—have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated and cytokine gene expression, and axonal regeneration after chronic SCI. Scar removal was conducted through a single incision with a double-bladed scalpel along the stump, and scar renewal was halted by adding α,α′-dipyridyl.ResultsDuring the chronic injury stage, two experiments were undertaken. The first experiment was aimed at testing the therapeutic effect of INDP combined with scar removal. Sixty days after therapeutic intervention, the expression of genes encoding for TNFα, IFNγ, IL4, TGFβ, BDNF, IGF1, and GAP43 was evaluated at the site of injury. Tyrosine hydroxylase and 5-hydroxytryptamine positive fibers were also studied. Locomotor evaluations showed a significant recovery in the group treated with scar removal + INDP. Moreover; this group presented a significant increase in IL4, TGFβ, BDNF, IGF1, and GAP43 expression, but a decrease of TNFα and IFNγ. Also, the spinal cord of animals receiving both treatments presented a significant increase of serotonergic and catecholaminergic fibers as compared to other the groups. The second experiment compared the results of the combined approach versus INDP alone. Rats receiving INDP likewise showed improved motor recovery, although on a lesser scale than those who received the combined treatment. An increase in inflammation and regeneration-associated gene expression, as well as in the percentage of serotonergic and catecholaminergic fibers was observed in INDP-treated rats to a lesser degree than those in the combined therapy group.ConclusionsThese findings suggest that INDP, both alone and in combination with scar removal, could modify the non-permissive microenvironment prevailing at the chronic phase of SCI, providing the opportunity of improving motor recovery.

show abstract

Immunization with neural-derived antigens inhibits lipid peroxidation after spinal cord injury

Cited by 39 publications

References 23 publications

Autoreactivity against myelin basic protein in patients with chronic paraplegia

Autoreactivity against myelin basic protein in patients with chronic paraplegia

Development of Protective Autoimmunity by Immunization with a Neural-Derived Peptide Is Ineffective in Severe Spinal Cord Injury

Immunization with neural derived peptides plus scar removal induces a permissive microenvironment, and improves locomotor recovery after chronic spinal cord injury

Contact Info

Product

Resources

About