Control of hypothalamic neuroendocrine interactions

El hipotálamo juega en los mamíferos superiores un papel central en la integración de funciones vitales como la regulación del metabolismo energético global, la saciedad y el hambre, el control de la presión sanguínea y la temperatura corporal, la sed, hidratación y metabolismo salino del organismo, y las funciones testiculares y ováricas, entre otras. Muchas de estas funciones neuroendocrinas se realizan mediante el control del funcionamiento de la hipófisis, utilizando un complejo sistema de retroalimentación que modula la secreción de una gran variedad de hormonas hipofisarias con efectos sistémicos de vital importancia, incluyendo las hormonas tiroideas o la hormona del crecimiento, entre otras. El hipotálamo consta de aproximadamente una docena de subestructuras, conocidas como núcleos hipotalámicos, que se encargan de controlar los diversos procesos. Hasta muy recientemente no ha sido posible evaluar la función hipotalámica directamente in vivo, un aspecto que se resolvía mediante procedimientos indirectos como la determinación de cambios en el peso corporal, eliminación de líquidos, alteraciones en la termorregulación o desequilibrios en el perfil de hormonas en sangre. En esta revisión describiremos toda una nueva serie de métodos de imagen no invasiva para la evaluación directa de la función hipotalámica y su impacto potencial en nuestro conocimiento actual de la regulación de las interacciones neuroendocrinas, con especial referencia a la regulación hipotalámica del apetito in vivo.Este trabajo ha sido financiado en parte por las ayudas: SAF-2008-01327, SAF2011-23622 del Ministerio de Economía y Competitividad y S2010/BMD-2349 de la Comunidad de Madrid concedidas a Sebastián Cerdán y la beca predoctoral BES 2009-027615 del Ministerio de Economía y Competitividad concedida a Blanca Lizarbe.Peer Reviewe

Editorial: “Transcellular Cycles Underlying Neurotransmission”

Peer reviewedPeer Reviewe

13C MRS: An outstanding tool for metabolic studies

We provide an overview of 13C magnetic resonance spectroscopy methods and their applications as an established metabolic tool with an emphasis on the use of high-resolution 13C magnetic resonance spectroscopy and 13C isotopomer analysis. Topics addressed include general properties of the 13C magnetic resonance spectroscopy spectrum; different 13C magnetic resonance spectroscopy acquisition protocols; determination of fractional 13C enrichment, kinetic, or steady state measurements of metabolic flux; 13C isotopomer analysis approaches; 13C(2H) magnetic resonance spectroscopy methodologies; and in vivo 13C magnetic resonance spectroscopy. Some illustrative applications are described. © 2005 Wiley Periodicals, Inc. Concepts Magn Reson Part A 27A: 1-16, 2005

Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic anti-inflammatory formulations

This work are distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery.This work was supported in part by grants from SOLUTEX SL to SC, grants from the Spanish Ministry of Economy and Competitivity SAF2011-23622, IPT-2012-1331-006000 to SC, grant CTQ2013-47669-R to PB, and grant S2010/BMD-2349 from the Community of Madrid to S.C. and P.B. D.C. and V.N. held predoctoral contracts from Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC).Peer Reviewe

Control hipotalámico de las interacciones neuroendocrinas

The hypothalamus plays in higher mammals a central role in the integration of vital functions as the regulation of global energy metabolism, satiety and hunger, the control of blood pressure and body temperature, thirst, hydration and electrolyte metabolism, testicular and or ovarian functions, among others. Many of these neuroendocrine functions are performed through the control of the performance of the hypophysis, using a complex system of feed- back loops that modulate the secretion of large variety of hypophysary hormones with systemic effects of vital importance, including the thyroid and growth hormones, among others. The hypothalamus has approximately a dozen of substructures, known as hypothalamic nuclei, which control the different processes. Until very recently, it has not been possible to evaluate directly the hypothalamic function in vivo, an aspect solved through indirect measurements as the determination of bodyweight changes, liquid elimination and alterations in thermoregulation or disequilibria in the hormonal profiles in blood. In this review we shall describe a novel series of non-invasive imaging and spectroscopy methods for the direct evaluation of hypothalamic function and their potential impact on our current knowledge of neuroendocrine regulation, with special reference to the hypothalamic regulation of appetite in vivo.El hipotálamo juega en los mamíferos superiores un papel central en la integración de funciones vitales como la regulación del metabolismo energético global, la saciedad y el hambre, el control de la presión sanguínea y la temperatura corporal, la sed, hidratación y metabolismo salino del organismo, y las funciones testiculares y ováricas, entre otras. Muchas de estas funciones neuroendocrinas se realizan mediante el control del funcionamiento de la hipófisis, utilizando un complejo sistema de retroalimentación que modula la secreción de una gran variedad de hormonas hipofisarias con efectos sistémicos de vital importancia, incluyendo las hormonas tiroideas o la hormona del crecimiento, entre otras. El hipotálamo consta de aproximadamente una docena de subestructuras, conocidas como núcleos hipotalámicos, que se encargan de controlar los diversos procesos. Hasta muy recientemente no ha sido posible evaluar la función hipotalámica directamente in vivo, un aspecto que se resolvía mediante procedimientos indirectos como la determinación de cambios en el peso corporal, eliminación de líquidos, alteraciones en la termorregulación o desequilibrios en el perfil de hormonas en sangre. En esta revisión describiremos toda una nueva serie de métodos de imagen no invasiva para la evaluación directa de la función hipotalámica y su impacto potencial en nuestro conocimiento actual de la regulación de las interacciones neuroendocrinas, con especial referencia a la regulación hipotalámica del apetito in vivo

MR imaging features of high-grade gliomas in murine models: How they compare with human disease, reflect tumor biology, and play a role in preclinical trials

Murine models are the most commonly used and best investigated among the animal models of HGG. They constitute an important weapon in the development and testing of new anticancer drugs and have long been used in preclinical trials. Neuroimaging methods, particularly MR imaging, offer important advantages for the evaluation of treatment response: shorter and more reliable treatment end points and insight on tumor biology and physiology through the use of functional imaging DWI, PWI, BOLD, and MR spectroscopy. This functional information has been progressively consolidated as a surrogate marker of tumor biology and genetics and may play a pivotal role in the assessment of specifically targeted drugs, both in clinical and preclinical trials. The purpose of this Research Perspectives was to compile, summarize, and critically assess the available information on the neuroimaging features of different murine models of HGGs, and explain how these correlate with human disease and reflect tumor biology.This work was supported by the Programme for Advanced Medical Education from Fundaçâo Champalimaud, Fundaçâo Calouste Gulbenkian, Ministério da Saúde and Fundaçâo para a Ciência e Tecnologia, Portugal, to the first author (A.R.B.), and by grants from the Spanish Ministry of Science and Innovation SAF 2008–01327 and the Community of Madrid S-BIO-2006–0170, to the last author (S.G.C.).Peer Reviewe

MR imaging features of high-grade gliomas in murine models: How they compare with human disease, reflect tumor biology, and play a role in preclinical trials

Murine models are the most commonly used and best investigated among the animal models of HGG. They constitute an important weapon in the development and testing of new anticancer drugs and have long been used in preclinical trials. Neuroimaging methods, particularly MR imaging, offer important advantages for the evaluation of treatment response: shorter and more reliable treatment end points and insight on tumor biology and physiology through the use of functional imaging DWI, PWI, BOLD, and MR spectroscopy. This functional information has been progressively consolidated as a surrogate marker of tumor biology and genetics and may play a pivotal role in the assessment of specifically targeted drugs, both in clinical and preclinical trials. The purpose of this Research Perspectives was to compile, summarize, and critically assess the available information on the neuroimaging features of different murine models of HGGs, and explain how these correlate with human disease and reflect tumor biology.This work was supported by the Programme for Advanced Medical Education from Fundaçâo Champalimaud, Fundaçâo Calouste Gulbenkian, Ministério da Saúde and Fundaçâo para a Ciência e Tecnologia, Portugal, to the first author (A.R.B.), and by grants from the Spanish Ministry of Science and Innovation SAF 2008–01327 and the Community of Madrid S-BIO-2006–0170, to the last author (S.G.C.).Peer Reviewe

Anysotropic relaxivity measurements of solubilized multiwall carbon nanotubes suspensions reveal molecular orientation

Trabajo presentado al 20th Annual Meeting & Exhibition International Society for Magnetic Resonance in Medicine, celebrado en Melbourne (Australia) del 5 al 11 de Mayo de 2012.Peer Reviewe

Time course of early metabolic changes following diffuse traumatic brain injury in rats as detected by 1H NMR spectroscopy

Experimental models of traumatic brain injury (TBI) provide a useful tool for understanding the cerebral metabolic changes induced by this pathological condition. Here, we report on the time course of changes in cerebral metabolites after TBI and its correlation with early brain morphological changes using a combination of high-resolution proton magnetic resonance spectroscopy ( 1H MRS) and magnetic resonance imaging (MRI). Adult male Sprague-Dawley rats were subjected to closed head impact and examined by MRI at 1, 9, 24, 48, and and 72 h after the injury. Extracts from funnel frozen rat brains were then obtained and analyzed quantitatively by high-resolution 1H MRS. Finally, statistical multivariate analysis was carried out to identify the combination of cerebral metabolites that best described the time evolution of diffuse TBI. The temporal changes observed in the concentration of cerebral metabolites followed three different patterns. The first pattern included taurine, threonine, and glycine, with concentrations peaking 24 h after the injury. The second pattern included glutamate, GABA, and alanine, with concentrations remaining elevated between 24 and 48 h post-injury. The third one involved creatine-phosphocreatine, N-acetylaspartate, and myo-inositol, with concentrations peaking 48 h after the injury. A multivariate stepwise discriminant analysis revealed that the combination of the organic osmolytes taurine and myo-inositol allowed optimal discrimination among the different time groups. Our findings suggest that the profile of some specific brain molecules that play a role as organic osmolytes can be used to follow-up the progression of the early diffuse brain edema response induced by TBI. © Mary Ann Liebert, Inc.This work was partly supported by Spanish Ministry of Education and Science (grants SAF 2001-224 and SAF 2004-03197 to J.M.R. and S.C.) and by Spanish Ministry of Health (grants FISss C03/08, C03/10, and G03/155 to J.M.R. and S.C.).Peer Reviewe