The vasodilator naftidrofuryl attenuates short-term brain glucose hypometabolism in the lithium-pilocarpine rat model of status epilepticus without providing neuroprotection

Status epilepticus (SE) triggered by lithium-pilocarpine is a model of epileptogenesis widely used in rats, reproducing many of the pathological features of human temporal lobe epilepsy (TLE). After the SE, a silent period takes place that precedes the occurrence of recurrent spontaneous seizures. This latent stage is characterized by brain glucose hypometabolism and intense neuronal damage, especially at the hippocampus. Importantly, interictal hypometabolism in humans is a predictive marker of epileptogenesis, being correlated to the extent and severity of neuronal damage. Among the potential mechanisms underpinning glucose metabolism impairment and the subsequent brain damage, a reduction of cerebral blood flow has been proposed. Accordingly, our goal was to evaluate the potential beneficial effects of naftidrofuryl (25 mg/kg i.p., twice after the insult), a vasodilator drug currently used for circulatory insufficiency-related pathologies. Thus, we measured the effects of naftidrofuryl on the short-term brain hypometabolism and hippocampal damage induced by SE in rats. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) neuroimaging along with various neurohistochemical assays aimed to assess brain damage were performed. SE led to both severe glucose hypometabolism in key epilepsy-related areas and hippocampal neuronal damage. Although naftidrofuryl showed no anticonvulsant properties, it ameliorated the short-term brain hypometabolism induced by pilocarpine. Strikingly, the latter was neither accompanied by neuroprotective nor by anti-inflammatory effects. We suggest that naftidrofuryl, by acutely enhancing brain blood flow around the time of SE improves the brain metabolic state but this effect is not enough to protect from the damage induced by SE

Diseño y elaboración de herramientas metodológicas para incorporar contenidos de ciencia y técnicas en el aula.

Depto. de Investigación y Psicología en EducaciónFac. de EducaciónFALSEsubmitte

Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease

Several cannabinoids afforded neuroprotection in experimental models of Huntington’s disease (HD). We investigated whether a 1:1 combination of botanical extracts enriched in either ∆9-tetrahydrocannabinol (∆9-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex®, is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD. We recorded the progression of neurological deficits and the extent of striatal deterioration, using behavioral, in vivo imaging, and biochemical methods in R6/2 mice and their corresponding wild-type mice. The mice were daily treated, starting at 4 weeks after birth, with a Sativex-like combination of phytocannabinoids (equivalent to 3 mg/kg weight of pure CBD + ∆9-THC) or vehicle. R6/2 mice exhibited the characteristic deterioration in rotarod performance that initiated at 6 weeks and progressed up to 10 weeks, and elevated clasping behavior reflecting dystonia. Treatment with the Sativex-like combination of phytocannabinoids did not recover rotarod performance, but markedly attenuated clasping behavior. The in vivo positron emission tomography (PET) analysis of R6/2 animals at 10 weeks revealed a reduced metabolic activity in the basal ganglia, which was partially attenuated by treatment with the Sativex-like combination of phytocannabinoids. Proton nuclear magnetic resonance spectroscopy (H+-MRS) analysis of the ex vivo striatum of R6/2 mice at 12 weeks revealed changes in various prognostic markers reflecting events typically found in HD patients and animal models, such as energy failure, mitochondrial dysfunction, and excitotoxicity. Some of these changes (taurine/creatine, taurine/N-acetylaspartate, and N-acetylaspartate/choline ratios) were completely reversed by treatment with the Sativex-like combination of phytocannabinoids. A Sativex-like combination of phytocannabinoids administered to R6/2 mice at the onset of motor symptoms produced certain benefits on the progression of striatal deterioration in these mice, which supports the interest of this cannabinoid-based medicine for the treatment of disease progression in HD patients

Análisis de resultados de investigación sobre la ciencia presente en la sociedad y su incorporación al aula

Este Proyecto de Innovación Docente es continuación de los proyectos anteriores PIE 43/2017-18, PIE 39/2018-19 y PIE 179/2019-20; y está en relación directa con el Proyecto I+D+i Identificación de contextos científicos en la sociedad. Herramientas para docentes y ciudadanos (RTI2018-094303-A-I00 del Ministerio de Economía y Competitividad, correspondiente al Programa Estatal de I+D+i Orientada a los Retos de la Sociedad, en el marco del Plan Estatal de Investigación Científica y Técnica y de Innovación 2019-21). También con el Proyecto FFI2015-64529, «La frontera entre ciencia y política y la ciencia en la frontera: la ciencia española, 1907-1975» del MINECO. Todos estos proyectos han venido realizándose con participación de por varios de los profesores del Grupo de Investigación UCM-970762 NEURODIDÁCTICA, CIENCIA Y SOCIEDAD. La finalidad última de la propuesta que se presenta ahora, es analizar los datos obtenidos en estos proyectos anteriores. Además, existen otros cinco de objetivos. En suma, buscamos: (1) analizar los datos obtenidos en los proyectos anteriores; (2) revisar las herramientas metodológicas utilizadas para la obtención de estos datos; (3) tomar en consideración otros modos paramétricos para medir la percepción sobre la ciencia; (4) fomentar la participación de nuestros estudiantes, y futuros docentes, en los procesos de análisis de resultados de investigación; y (5) incorporar a nuestros estudiantes y alguna de sus propuestas como una más de las actividades realizadas por el Museo Nacional de Ciencias Naturales. Este último objetivo se interrumpió en el proyecto anterior, en marzo del 2020, debido a las circunstancias causadas por la el covid-19, lo que nos invita a plantearnos, también, (6) fundamentar en los conocimientos y datos científicos la toma de decisiones personales y comunitarias frente a bulos y desinformaciones