Efectos del tratamiento con Compvit B, ácido orótico o la combinación de ambos sobre la recuperación de la memoria espacial en ratas con lesión de fimbria-fornix Effects of treatment with Compvit B, orotic acid or their combination on the recovery of spatial memory in rats with fimbria-fornix lesion

Las vitaminoterapias han sido ampliamente utilizadas en neurología para el tratamiento de neuritis o la correción de déficit metabólicos. En Cuba, se produce desde hace algunos años el preparado vitamínico Compvit®, que contiene vitaminas B1, B6 y B12. El ácido orótico, también llamado vitamina B13, es un producto natural que ha mostrado acciones como nootrópico en estudios con animales jóvenes y viejos que acusan deterioro cognitivo. En el presente trabajo se reportan los resultados de un estudio realizado para evaluar las potencialidades terapéuticas del Compvit® y del ácido orótico, empleando la lesión del sistema fimbria-fornix, que afecta severamente las capacidades de aprendizaje de los animales. Los resultados confirman un efecto positivo de cada uno de los tratamientos vitamínicos mejorando las capacidades cognitivas afectadas por la lesión. Aunque ninguno de los productos empleados o su combinación fue capaz de elevar el rendimiento cognitivo al nivel de los animales sanos, todos logran mejorías signficativas en comparación con el placebo. Este trabajo constituye una evidencia adicional en favor del uso terapéutico de compuestos vitamínicos como parte del tratamiento neurorrestaurativo.Vitamin therapies have been widely used in Neurology for the treatment of neuritis or the correction of metabolic deficits. In Cuba, Compvit® (B1, B6 and B12 vitamins) have been produced since several years. Orotic acid, also called vitamin B13 is a natural product showing nootropic actions in studies with young and old cognitively impaired animals. The present paper reports the results of a study conducted to assess the therapeutic potentials of Compvit® and orotic acid, in the recovery of cognitive abilities in fimbria-fornix lesioned animals, a lesion known to severely impair learning abilities. The results confirm positive effects of each vitamin treatment to improve the cognitive abilities affected by lesion. Although none of the products used, neither their combination, was able to raise the cognitive performance to the level of non-lesioned animals, both of them achieve significant improvement compared to placebo. The present paper constitutes additional evidence favoring the therapeutic use of vitamin compounds as part of neurorestorative treatments

Evaluación de la ficocianobilina y sus combinaciones en un modelo animal de esclerosis múltiple

INTRODUCTION: Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by generalized areas of focal demyelination. The mainly used animal model is experimental autoimmune encephalomyelitis.OBJECTIVE: To demonstrate the effects of treatment with phycocyanobilin and their combinations. The PCB is a biliproteina derived from the cyanobacteria Spirulina platensis.METHODS: EAE was induced in mice C57BL / 6 with MOG35-55 in adjuvant full of Freund/emulsion of Mycobacterium tuberculosis and pertussis toxin. In this model was evaluated the effect of PCB/IFNbeta compared with the active ingredients in an independent way. The daily clinical progression was evaluated, and the concentrations of CCL5, CXCL10, IFN-γ, CXCL2, CCL2, IL-17A, IL-6 and IL-10 in homogenized tissue were determined by ELISA.RESULTS: EAE mice treated with the PCB/IFN-beta combination showed a significant decrease of the clinical score. On the other hand, PCB/IFN-beta combination treatment induced a significant decrease in the levels of IL-10 and IL-17 in homogenized's brain.CONCLUSION: The PCB/IFN-beta combination reduces the clinical progression of disease EAE, an effect possibly mediated in the brain by a decrease in the levels of IL-17A and IL-10.INTRODUCCIÓN: La esclerosis múltiple es una enfermedad inflamatoria crónica del sistema nervioso central caracterizada por áreas generalizadas de desmielinización focal. El modelo animal principalmente utilizado es la encefalomielitis autoinmune experimental.OBJETIVO: Demostrar los efectos del tratamiento con ficocianobilina y sus combinaciones. La PCB es una biliproteína derivada de la cianobacteria Spirulina platensis.MÉTODOS: Se indujo EAE en ratones C57BL / 6 con MOG35–55 en adyuvante completo de Freund/emulsión de Mycobacterium tuberculosis y la toxina pertussis. En este modelo fue evaluado el efecto de la PCB/IFNbeta en comparación con los ingredientes activos de forma independiente. La progresión clínica diaria fue evaluada, y se determinaron, mediante ELISA, las concentraciones de CCL5, CXCL10, IFN–γ, CXCL2, CCL2, IL–17A, IL–6 e IL–10 en homogeneizados de tejido.RESULTADOS: Los ratones con EAE tratados con la combinación PCB/IFN–beta mostraron una disminución significativa de la puntuación clínica. Por otro lado, el tratamiento de combinación PCB/IFN–beta indujo una disminución significativa de los niveles de IL–10 y IL–17 en homogeneizados de cerebro.CONCLUSIÓN: La combinación PCB/IFN–beta aminora la progresión clínica de la enfermedad EAE, un efecto posiblemente mediado en el cerebro por una disminución de los niveles de IL–17A e IL–10

Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study.

Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO) are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO) is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV) and grey matter volumes (GMV) and/or perfusion on one side, and the number of optic neuritis (ON) attacks, myelitis attacks and/or total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO

Brain perfusion positive correlation with the number of optic neuritis attacks in RNMO patients.

<p>The same slices as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066271#pone-0066271-g001" target="_blank">Figure 1</a>, presenting the perfusion positive correlation statistical parametric map, which was found in an extensive brain area mainly located in the white matter. Note that perfusion changes included periventricular areas. Statistical parametric map was thresholded at p value <0.01 (p value <0.05 corrected for multiple comparisons at the cluster level).</p

Demographic and clinical characteristics of patients with relapsing neuromyelitis optica (n = 15).

<p>Data shown as median and range (minimum, maximum). EDSS, Kurtzke Expanded Disability Status Scale <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066271#pone.0066271-Kurtzke1" target="_blank">[24]</a>; ON, optic neuritis; LETM, longitudinally extensive transverse myelitis; NMO-IgG, antiaquaporin-4 autoantibody;</p>*<p>Last attack MRI/SPECT time interval.</p

Multimodal negative correlation pattern with the number of optic neuritis attacks in RNMO patients.

<p>Axial, sagittal and coronal selected slices at four brain levels (levels shown as white lines in the figures on the right side), presenting overlays of negative correlation statistical parametric maps of white matter volume (in green), grey matter volume (in blue) and perfusion (in pink) on a T1-weighted high resolution MRI template. Decreases of tissue volumes and perfusion with the increase of the number of optic neuritis attacks comprised extensive brain regions, including important components of the visual system such as posterior thalamic radiations (white matter volume), middle and superior temporal gyri (grey matter volume) and the primary visual area (perfusion). Also note that tissue volume decreases included regions close to periaqueductal areas. Statistical parametric maps were thresholded at p value <0.01 (p value <0.05 corrected for multiple comparisons at the cluster level).</p

Brain regions with negative correlation between grey matter volume and the number of optic neuritis attacks.

<p>P, P value corrected for multiple comparisons at cluster level; GM, grey matter.</p

Brain regions with positive correlation between perfusion and the number of optic neuritis attacks.

<p>P, P value corrected for multiple comparisons at cluster level; DWM, deep white matter; SWM, superficially located white matter; GM, grey matter.</p

Brain regions with negative correlation between white matter volume and the number of optic neuritis attacks.

<p>P, P value corrected for multiple comparisons at cluster level; DWM, deep white matter; SWM, superficially located white matter.</p