Delayed injection of polypyrrole doped with iodine particle suspension after spinal cord injury in rats improves functional recovery and decreased tissue damage evaluated by 3.0 Tesla in vivo magnetic resonance imaging
Mondragon-Lozano R.,Instituto Nacional de Investigaciones Nucleares |
Rios C.,Instituto Nacional Of Neurologia Y Neurocirugia Manuel Velasco Suarez Ssa |
Roldan-Valadez E.,Panamerican University of Mexico |
Cruz G.J.,Instituto Nacional de Investigaciones Nucleares |
And 10 more authors.
Spine Journal | Year: 2016
Background Context: Traumatic spinal cord injury (SCI) causes irreversible damage with loss of motor, sensory, and autonomic functions. Currently, there is not an effective treatment to restore the lost neurologic functions. Purpose: Injection of polypyrrole-iodine(PPy-I) particle suspension is proposed as a therapeutic strategy. Study Design: This is an in vivo animal study. Methods: This study evaluates the use of such particles in rats after SCI by examining spared nervous tissue and the Basso, Beattie, and Bresnahan (BBB) scale to evaluate the functional outcome. Diffusive magnetic resonance imaging (MRI) was employed to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) as non-invasive biomarkers of damage after SCI. Results: Fractional anisotropy decreased, whereas ADC increased in all groups after the lesion. There were significant differences in FA when compared with the SCI-PPy-I group versus the SCI group (p<.05). Significant positive correlations between BBB and FA (r2=0.449, p<.05) and between FA and preserved tissue (r2=0.395, p<.05) were observed, whereas significant negative associations between BBB and ADC (r2=0.367, p<.05) and between ADC and preserved tissue (r2=0.421, p<.05) were observed. Conclusions: The results suggested that PPy-I is neuroprotective as it decreased the amount of damaged tissue while improving the motor function. Non-invasive MRI proved to be useful in the characterization of SCI and recovery. © 2016 Elsevier Inc.
PubMed | National Autonomous University of Mexico, Hospital Of Pediatria Cmn Siglo Xxi, UIMEN, Laboratory Bioenergetica y Envejecimiento Celular and 2 more.
Type: Journal Article | Journal: BMC neuroscience | Year: 2017
Immunization 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 ,-dipyridyl.During 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 TNF, IFN, IL4, TGF, 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, TGF, BDNF, IGF1, and GAP43 expression, but a decrease of TNF and IFN. 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.These 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.
Zajarias-Fainsod D.,Anahuac University of North Mexico |
Carrillo-Ruiz J.,Anahuac University of North Mexico |
Carrillo-Ruiz J.,Hospital General Of Mexico Od |
Mestre H.,Anahuac University of North Mexico |
And 6 more authors.
European Spine Journal | Year: 2012
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 (colorimetric- BrdU 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. © 2011 Springer-Verlag.
Martinon S.,Research Center Del Proyecto Camina Ac |
Garcia E.,Research Center Del Proyecto Camina Ac |
Garcia E.,Anahuac University of North Mexico |
Gutierrez-Ospina G.,National Autonomous University of Mexico |
And 3 more authors.
PLoS ONE | Year: 2012
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 (T A91) 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 T A91 cells which predominantly showed to have a Th2 phenotype capable of producing BDNF, further promoting neuroprotection. © 2012 Martiñón et al.
Rodriguez-Barrera R.,Anahuac University of North Mexico |
Rodriguez-Barrera R.,Metropolitan Autonomous University |
Rodriguez-Barrera R.,Research Center Del Proyecto Camina Ac |
Fernandez-Presas A.M.,National Autonomous University of Mexico |
And 14 more authors.
BioMed Research International | Year: 2013
Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC) injury. Immunization with neural-derived peptides (INDPs) such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group). Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-α). To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-α concentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy. © 2013 Roxana Rodríguez-Barrera et al.
Gonzalez-Torres M.,Instituto Nacional de Investigaciones Nucleares |
Gonzalez-Torres M.,National Autonomous University of Mexico |
Cruz-Cruz G.J.,Instituto Nacional de Investigaciones Nucleares |
Sanchez-Mendieta V.,National Autonomous University of Mexico |
And 7 more authors.
Polymer Bulletin | Year: 2016
A study on dapsone uptake and release model in plasma polypyrrole for drug administration in the central nervous system is presented in this work. The polymer was treated by lyophilization to induce pores on the surface that housed the drug. After that, the polymer was immersed in dapsone–ethanol solutions at different concentrations to introduce the drug into the pores, which once filled the pores, covered the polymer particles. The release of dapsone was tested in water and Krebs–Ringer solutions measured by UV–Vis spectroscopy considering surrounding static and dynamic fluids. The release in both models increased with the contact time in the fluids following linear tendencies. In all cases, the dissolution of the outer dapsone layer of the polymer particles occurred in the first 5 min, which was approximately 10 % of the total dapsone loaded. Dapsone was released at a higher rate in KR solutions than in water, which suggests that the ions of the KR salts help in this process. Morphology and chemical structures are studied before and after adding the drug to the polymer. © 2016 Springer-Verlag Berlin Heidelberg