Brain immune interactions after stroke

Trabajo presentado en el XVIIth International Congress of Neuropathology celebrado en Salzburgo, Austria, del 11 al 15 de septiembre de 2010Peer reviewe

Inflammation and Immunity in Stroke

Comunicación presentada en Canadian Stroke Congress, celebrado del 2 al 4 de octubre de 2011 en Ottawa (Canadá). También se presentó una versión en Neuroscience Club Seminare, del Institut für Molekulare Regenerative Medizin (Paracelsus Medizinische Privatuniversität) el 14 de junio de 2012, en Salzburg (Austria)Peer Reviewe

Antigen-specific immune reactions to ischemic stroke

Brain proteins are detected in the cerebrospinal fluid (CSF) and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs) carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier (BBB) or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing recovery from stroke

Autophagy, and BiP level decrease are early key events in retrograde degeneration of motoneurons

El pdf del artículo es la versión post-print.-- et al.Disconnection of the axon from the soma of spinal motoneurons (MNs) leads either to a retrograde degenerative process or to a regenerative reaction, depending on the severity and the proximity to the soma of the axonal lesion. The endoplasmic reticulum (ER) is a continuous membranous network that extends from the nucleus to the entire cytoplasm of the neuronal soma, axon and dendrites. We investigated whether axonal injury is sensed by the ER and triggers the activation of protective mechanisms, such as the unfolded protein response (UPR) and autophagy. We found early (at 3 days) accumulation of beclin1, LC3II and Lamp-1, hallmarks of autophagy, in both degenerating MNs after spinal root avulsion and in non-degenerating MNs after distal nerve section, although Lamp-1 disappeared by 5 days only in the former. In contrast, only degenerating MNs presented early activation of IRE1α, revealed by an increase of the spliced isoform of Xbp1 and accumulation of ATF4 in their nucleus, two branches of the UPR, and late BiP downregulation in association with cytoskeletal and organelle disorganization. We conclude that BiP decrease is a signature of the degenerating process, as its overexpression led to an increase in MN survival after root avulsion. Besides, Bcl2 is strongly implicated in the survival pathway activated by BiP overexpression.This work was supported by grants from the Ministerio de Ciencia y Tecnologia (Grants SAF2006-08682, SAF2009-12495), the Ministerio de Sanidad (FIS PI081932) and funds from Red de Terapia Celular (TERCEL) and from the Centro de investigacion biomedica en Red para enfermedades neurodegenerativas (CIBERNED) of Spain.Peer Reviewe

Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Objective]: This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. [Methods]: Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. [Results]: Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. [Conclusions]: Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease. © 2012 Amigó-Correig et al.This work was supported by project no SAF 2006-07382 and grant no BES-2007-17284, both awarded by the Spanish Ministry of Education of Science, and by project noCP07/00152, financed by the Carlos III Health Institute (ISCIII). Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas is an initiative of ISCIII (Ministerio de Ciencia e Innovacion).Peer Reviewe

Evaluación participativa del empoderamiento juvenil con grupos de jóvenes : análisis de casos

Las interpretaciones que realizan los jóvenes sobre sus propias realidades son clave para comprender sus acciones y comportamientos. También para adaptar los proyectos y programas socioeducativos a las nuevas dinámicas sociales. Este artículo se centra en el análisis de dichas interpretaciones. ¿Qué entienden los jóvenes por empoderamiento juve­nil? ¿Qué indicadores específicos consideran que permiten identificarlo? ¿En qué espacios, momentos y procesos piensan que se produce? Para dar respuesta a estos interrogantes se realizaron 4 procesos de Evaluación Participativa con 42 jóvenes, de entre 14 y 25 años, en 4 ciudades españolas. La muestra de jóvenes que configura los grupos de evaluación parti­cipativa en cada uno de los casos es intencional. El artículo contextualiza los casos, presenta la metodología seguida en el desarrollo de la evaluación participativa y aporta los resultados principales de cada caso. Los resultados muestran que los jóvenes de los casos analizados relacionan el empoderamiento con algún tipo de enriquecimiento o mejora de tipo perso­nal o grupal normalmente asociado a un proceso personal, aunque se reconoce la influencia social. Los indicadores considerados más relevantes para el empoderamiento juvenil son la autonomía y la autoestima. Los jóvenes relacionan el empoderamiento juvenil con espacios vinculados al ámbito familiar, escolar y con las amistades. Según las características de los gru­pos aparecen también como significativos; el espacio extracurricular, la calle y el mundo aso­ciativo. Los procesos de empoderamiento juvenil tienen que ver con vivencias de superación que hicieron que los jóvenes tuvieran percepción de éxito, de superación, de ser importantes para alguien o, por último, de sentir bienestar. La evaluación participativa ha resultado ser una estrategia de intervención socioeducativa muy adecuada para ayudar a las personas jóvenes participantes a construir perspectivas diferentes sobre sus propias vidasInterpretations made by young people about their own realities are key to understand their actions and behaviours. Also for adapting to new social dynamics socio-educational programmes and projects. This article focuses on the analysis of those interpretations. What do youth understand by youth empowerment? Which specific indicators do they consider to identify it? In which spaces, moments and processes do they think that it could happen? In order to respond to these questions, 4 evaluation participatory processes with 42 young people from 14 to 25 years old in 4 Spanish cities were developed. The sample that sets the participatory evaluation groups for every case is intentional. This paper contextualizes cases, presenting the followed methodology in the participatory evaluation's development and provides the main findings of each case. The results show that youth from the analyzed cases consider the empowerment to be related with a personal or group enrichment or improvement that is normally associated with a personal process, although its social influence is recognized. The most relevant indicators for youth empowerment are autonomy and self-esteem. Young people relate youth empowerment to spaces linked to family, school and friends. The extracurricular space, the street and the associative world appear to be significant to some of them. Youth empowerment processes have to do with overcoming experiences that made young people to have a perception of success, to overcome, being important to someone or eventually, to feel well being. Participatory evaluation has proved to be a very adequate socio-educational intervention strategy to help participants building different perspectives on their own live

The structures of youth participation in Catalonia since the democratic transition

Youth participation is and has been a concept with many considerations, meanings and forms of application, both nationally and internationally. In order to ascertain the evolution of the main structures of youth participation, this article starts with the frames that have motivated this participation in Europe, and then it analyses the evolution of some of the participative youth structures in Catalonia in recent decades: local and municipal youth councils. The article also examines some of the longstanding challenges of youth participation, which aim to overcome the structuring of traditional channels of participation and generate other ways of taking part in everyday community life

Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide

[Background] Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS.[Methods] Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA. Cells were treated with PGE2, and the effect on LPS-induced expression of TNF-α messenger RNA (mRNA) and protein was studied in the presence or absence of drug antagonists of the four EP receptors. EP receptor expression and the effects of EP2 and EP4 agonists and antagonists were studied at different time points after LPS.[Results] PGE2 production after LPS was COX-2-dependent. PGE2 reduced the glial production of TNF-α after LPS. Microglia expressed higher levels of EP4 and EP2 mRNA than astroglia. Activation of EP4 or EP2 receptors with selective drug agonists attenuated LPS-induced TNF-α in microglia. However, only antagonizing EP4 prevented the PGE2 effect demonstrating that EP4 was the main target of PGE2 in naïve microglia. Moreover, the relative expression of EP receptors changed during the course of classical microglial activation since EP4 expression was strongly depressed while EP2 increased 24 h after LPS and was detected in nuclear/peri-nuclear locations. EP2 regulated the expression of iNOS, NADPH oxidase-2, and vascular endothelial growth factor. NADPH oxidase-2 and iNOS activities require the oxidation of NADPH, and the pentose phosphate pathway is a main source of NADPH. LPS increased the mRNA expression of the rate-limiting enzyme of the pentose pathway glucose-6-phosphate dehydrogenase, and EP2 activity was involved in this effect.[Conclusions] These results show that while selective activation of EP4 or EP2 exerts anti-inflammatory actions, EP4 is the main target of PGE2 in naïve microglia. The level of EP receptor expression changes from naïve to primed microglia where the COX-2/PGE2/EP2 axis modulates important adaptive metabolic changes.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) (SAF2014-56279R) and the European Community FP7 (InMiND project no. 278850). EBT had an FPU PhD fellowship of MINECO.Peer reviewe

Aplicació de la metodologia POGIL a l'aprenentatge de la fisiologia

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524POGIL és l’acrònim de “Process Oriented Guided Inquiry Learning”. És una metodologia que encaixa amb el constructivisme: l’estudiant construeix el coneixement a partir de qüestions i tasques proposades pel professor. Una activitat POGIL consisteix en una sessió a l’aula en la que els estudiants treballen sobre un qüestionari amb activitats diverses, de forma que al final són ells mateixos els que elaboren el tema..

IL-10 regulates adult neurogenesis by modulating ERK and STAT3 activity

The adult subventricular zone (SVZ) contains Nestin+ progenitors that differentiate mainly into neuroblasts. Our previous data showed that interleukin-10 (IL-10) regulates SVZ adult neurogenesis by up-regulating the expression of pro-neural genes and modulating cell cycle exit. Here we addressed the specific mechanism through which IL-10 carries out its signaling on SVZ progenitors. We found that,in vitro andin vivo, IL-10 targets Nestin+ progenitors and activates the phosphorylation of ERK and STAT3. The action of IL-10 on Nestin+ progenitors is reversed by treatment with a MEK/ERK inhibitor, thus restoring neurogenesis to normal levels. Silencing STAT3 expression by lentiviral vectors also impaired neurogenesis by blocking the effects of IL-10. Our findings unveil ERK and STAT3 as effectors of IL-10 in adult SVZ neurogenesis. © 2015, Frontiers Research Foundation. All rights reservedThis work was supported by Marató TV3, and Mapfre foundation to EP. EP was a researcher of the Ramón y Cajal program (MICINN Spain).Peer Reviewe