Astrocytes as Active Players of the Innate Immune System: Another Layer of Astroglial Heterogeneity?

Reactive gliosis involving activation and proliferation ofastrocytes and microglia is a widespread but largely complexand graded glial response to brain injury. Astroglial populationhas a previously underestimated high heterogeneitywith cells differing in their morphology, gene expressionprofile, and response to injury. Over the last years, wehave been studying whether astrocytes may behave as facultativeinnate immunity cells after central nervous systeminjury. Classical innate immunity activation in the absenceof infection relies on the damage-associated molecular patterns(DAMP) release by dying cells. DAMPs behave asligands of the pattern recognition receptors, such as Tolllikereceptor, RAGE, and others. Using a combination ofmathematical modeling, in vitro and in vivo experimentation,we have been able to show that astrocytes essentially behaveas facultative cells of the innate immunity response that classically follows brain damage.While classical innate immunitypathways such as those involving RAGE, Toll-like receptor4/nuclear factor-jB, and TREM-2 are activated byreleased DAMPs, astrocytes are also key players in determiningthe interaction with local and peripheral professionalimmune cells. Moreover, detailed histological studies andex vivo culture experiments have shown that only a subsetof astrocytes seems to have the immune and neuroinflammatoryrole in experimental focal brain lesions and they canbe specifically targeted by dendrimeric nanoparticles. Thisadditional layer of neurobiological complexity can also beexplored for therapeutic purposes oriented toward controllingneuroinflammation in the injured brain.Fil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaReunion Anual de la Sociedad Argentina de Investigacion en NeurocienciasArgentinaSociedad Argentina de Neurologi

Vertical stability of circular orbits in relativistic razor-thin disks

During the last few decades, there has been a growing interest in exact solutions of Einstein equations describing razor-thin disks. Despite the progress in the area, the analytical study of geodesic motion crossing the disk plane in these systems is not yet so developed. In the present work, we propose a definite vertical stability criterion for circular equatorial timelike geodesics in static, axially symmetric thin disks, possibly surrounded by other structures preserving axial symmetry. It turns out that the strong energy condition for the disk stress-energy content is sufficient for vertical stability of these orbits. Moreover, adiabatic invariance of the vertical action variable gives us an approximate third integral of motion for oblique orbits which deviate slightly from the equatorial plane. Such new approximate third integral certainly points to a better understanding of the analytical properties of these orbits. The results presented here, derived for static spacetimes, may be a starting point to study the motion around rotating, stationary razor-thin disks. Our results also allow us to conjecture that the strong energy condition should be sufficient to assure transversal stability of periodic orbits for any singular timelike hypersurface, provided it is invariant under the geodesic flow.Comment: 13 pages, 4 figures; Accepted for publication in Physical Review

Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

With confirmed coronavirus disease 2019 (COVID-19) cases surpassing the 18 million mark around the globe, there is an imperative need to gain comprehensive understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are associated with respiratory or intestinal symptoms, reports of neurological signs and symptoms are increasing. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the central nervous system (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood–brain barrier. Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS rennin-angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for Middle East respiratory syndrome coronavirus (MERS-CoV). Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes, and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to disbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this comprehensive review, we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV; explore the potential role for astrocytes and microglia in the infection and neuroinflammation; and compare them with the previously described human and animal CoV that showed neurotropism to propose possible underlying mechanisms.Fil: Murta, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Convulsive Stress Mimics Brain Hypoxia and Promotes the P-Glycoprotein (P-gp) and Erythropoietin Receptor Overexpression. Recombinant Human Erythropoietin Effect on P-gp Activity

Erythropoietin (EPO) is not only a hormone that promotes erythropoiesis but also has a neuroprotective effect on neurons attributed to its known anti-apoptotic action. Previously, our group has demonstrated that recombinant-human EPO (rHu-EPO) can protect neurons and recovery motor activity in a chemical focal brain hypoxia model (Merelli et al., 2011). We and others also have reported that repetitive seizures can mimic a hypoxic- like condition by HIF-1α nuclear translocation and high neuronal expression P-gp. Here, we report that a single 20-min status epilepticus (SE) induces P-gp and EPO-R expression in cortical pyramidal neurons and only P-gp expression in astrocytes. In vitro, excitotoxic stress (300 μM glutamate, 5 min), can also induce the expression of EPO-R and P-gp simultaneously with both HIF-1α and NFkB nuclear translocation in primary cortical neurons. Primary astrocytes exposed to chemical hypoxia with CoCl2 (0.3 mM, 6 h) increased P-gp expression as well as an increased efflux of Rhodamine 123 (Rho123) that is a P-gp substrate. Tariquidar, a specific 3er generation P-gp-blocker was used as an efflux inhibitor control. Astrocytes treated with rHu-EPO showed a significant recovery of the Rho123 retention in a similar way as seen by Tariquidar, demonstrating for first time that rHu-EPO can inhibit the P-gp-dependent efflux activity. Taking together, these data suggest that stimulation of EPO depending signaling system could not only play a central role in brain cell protection, but this system could be a new tool for reverse the pharmacoresistant phenotype in refractory epilepsy as well as in other pharmacoresistant hypoxic brain diseases expressing P-gp.Fil: Merelli, Amalia Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Lazarowski, Alberto Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; ArgentinaFil: Auzmendi, Jerónimo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Coherent optical transduction of suspended microcapillary resonators for multi-parameter sensing applications

Characterization of micro and nanoparticle mass has become increasingly relevant in a wide range of fields, from materials science to drug development. The real-time analysis of complex mixtures in liquids demands very high mass sensitivity and high throughput. One of the most promising approaches for real-time measurements in liquid, with an excellent mass sensitivity, is the use of suspended microchannel resonators, where a carrier liquid containing the analytes flows through a nanomechanical resonator while tracking its resonance frequency shift. To this end, an extremely sensitive mechanical displacement technique is necessary. Here, we have developed an optomechanical transduction technique to enhance the mechanical displacement sensitivity of optically transparent hollow nanomechanical resonators. The capillaries have been fabricated by using a thermal stretching technique, which allows to accurately control the final dimensions of the device. We have experimentally demonstrated the light coupling into the fused silica capillary walls and how the evanescent light coming out from the silica interferes with the surrounding electromagnetic field distribution, a standing wave sustained by the incident laser and the reflected power from the substrate, modulating the reflectivity. The enhancement of the displacement sensitivity due to this interferometric modulation (two orders of magnitude better than compared with previous accomplishments) has been theoretically predicted and experimentally demonstrated

Editorial: Modulating glial cells phenotype. New findings and therapies

Aging and neurodegenerative diseases are closely related, and the common point between both scenarios is neuroinflammation. Neuroinflammation is mainly mediated by glial cells, astrocytes, and microglia; while endothelial cells transfer the pro-inflammatory signals from periphery. The mechanism that underlies glial cells activation and neuroinflammation-related damage is not fully understood, being the study of glial cells during aging as well as neurodegenerative diseases, a key point to identify targets and to develop therapies that modulate adverse outcomes and mitigate neurodegeneration. This Research Topic has produced a highly informative collection of original research and reviews, that cover multiple aspects for delving neuroinflammation and glial phenotypic changes in neurological diseases and aging. Researchers have presented their work and views to explain cellular and molecular mechanisms acquired by glial cells as well as possible interventions that can modify their functions and phenotypes associated with a broad spectrum of neurological diseases.Fil: Bellini, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Diz Chaves, Yolanda. Universidad de Vigo; EspañaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Análisis bibliométrico del proceso evolutivo del internet de las cosas

The current article presents a bibliometric anaylisis about the contribution made by the Internet of Things (IoT), from its appearance, viewed since social, academic and techonological levels. This analysis was carried out collecting information to a global standard, also it was reviewed more than 60.000 files, which are in the bibliogaphic database Scopus, by means of the techonological tool RStudio. This resource supports the processing of obtained data and whose main idea is to highlight the importance of different scientific and academic cooperations that are developed to national and international standard, which are focused on to research about this topic. It was used the method of information analysis, which consists in study design, data summary, proecessing and display, also the obtained results interpretation since the reckonings made through Rstudio. These results show that the IoT is a very important reference frame to its applicability in many production and services fields to a global level. It is also evident that the United States and China are nations that develop scientific production to a large-scale about the IoT, allocating a big quantity of human, physic and techological resources to such aim.El presente artículo presenta un análisis bibliométrico acerca de la contribución hecha por el Internet de las Cosas (IoT), desde su aparición, vista teniendo en cuenta, los niveles social, académico y tecnológico, este análisis fue desarrollado, recolectando información a nivel global, también se hizo una revisión de más de 60.000 documentos, las cuales están en la base de datos bibliográfica denominada Scopus, por medio de la herramienta tecnológica Rstudio. Este recurso apoya el procesamiento de datos obtenidos y cuya idea principal es resaltar la importancia de las diferentes contribuciones científicas y académicas que son realizadas a nivel nacional e internacional, que están dedicadas a la investigación sobre este tema. Se utilizó el método de análisis de información, que consiste en un estudio de diseño, recopilación, procesamiento y visualización de datos, también, la interpretación de resultados obtenidos, a partir de cálculos realizados a través de Rstudio. Estos resultados muestran que el IoT es un marco de referencia muy importante para su aplicabilidad en muchos campos de producción y servicios a un nivel global. También es evidente que naciones como los Estados Unidos y China desarrollan producción científica a gran escala, sobre el IoT, destinando una gran cantidad de recursos humanos, físicos y tecnológicos para tal fin

Análisis bibliométrico del proceso evolutivo del internet de las cosas

The current article presents a bibliometric anaylisis about the contribution made by the Internet of Things (IoT), from its appearance, viewed since social, academic and techonological levels. This analysis was carried out collecting information to a global standard, also it was reviewed more than 60.000 files, which are in the bibliogaphic database Scopus, by means of the techonological tool RStudio. This resource supports the processing of obtained data and whose main idea is to highlight the importance of different scientific and academic cooperations that are developed to national and international standard, which are focused on to research about this topic. It was used the method of information analysis, which consists in study design, data summary, proecessing and display, also the obtained results interpretation since the reckonings made through Rstudio. These results show that the IoT is a very important reference frame to its applicability in many production and services fields to a global level. It is also evident that the United States and China are nations that develop scientific production to a large-scale about the IoT, allocating a big quantity of human, physic and techological resources to such aim.El presente artículo presenta un análisis bibliométrico acerca de la contribución hecha por el Internet de las Cosas (IoT), desde su aparición, vista teniendo en cuenta, los niveles social, académico y tecnológico, este análisis fue desarrollado, recolectando información a nivel global, también se hizo una revisión de más de 60.000 documentos, las cuales están en la base de datos bibliográfica denominada Scopus, por medio de la herramienta tecnológica Rstudio. Este recurso apoya el procesamiento de datos obtenidos y cuya idea principal es resaltar la importancia de las diferentes contribuciones científicas y académicas que son realizadas a nivel nacional e internacional, que están dedicadas a la investigación sobre este tema. Se utilizó el método de análisis de información, que consiste en un estudio de diseño, recopilación, procesamiento y visualización de datos, también, la interpretación de resultados obtenidos, a partir de cálculos realizados a través de Rstudio. Estos resultados muestran que el IoT es un marco de referencia muy importante para su aplicabilidad en muchos campos de producción y servicios a un nivel global. También es evidente que naciones como los Estados Unidos y China desarrollan producción científica a gran escala, sobre el IoT, destinando una gran cantidad de recursos humanos, físicos y tecnológicos para tal fin

Astroglial phenotypes in traumatic brain injury and their relationship with neuronal degeneration

Astrocytes are key players in the Central Nervous System injury.By not completely defined pathways, reactive astrocytes may suffer a pathological remodeling engaging a pro-inflammatory phenotype that is very stable and promote further neuroinflammation andneurodegeneration. We here aimed to define the spatio-temporaldistribution of astroglial phenotypes after traumatic brain injury andthe consequences for neuronal survival and behavioral parameters.Following a stereotaxic stab wound injury (0.8 mm needle, coordinates 2 mm posterior and lateral to Bregma; 1 mm depth) performedin C57BL/6 mice and immunohistochemistry on brain sections, weclassified GFAP reactive astrocytes in five different phenotypes defined using Sholl analysis (Auzmendi et al., Molec. Neurobiol. 2019).While at 1 day post-injury (DPI) GFAP+ astrocytes were not differentfrom contralateral non-injured hemisphere, at 3DPI and 7DPI highly reactive phenotypes colocalized with altered neurons in lesionpenumbra. At 14DPI highly reactive astrocytes and altered neuronswere abundant only in the lesion core. Pro-inflammatory gain offunction paradigm was achieved by administering LPS (5 mg/Kg i.p)in lesioned animals, and that resulted in a greater number of complex reactive astrocytes at 7DPI (p<0.05) and a population of C3+astrocytes. On the other hand, loss of function paradigm with chemical NFkB blocker sulfasalazine (150 mg/kg i.p) significantly reducedhighly reactive astrocytes (p<0.05) and showed reduced neuronaldeath. Animal motor deficits were analyzed by computer-assistedopen field, but at 7DPI we were unable to detect significative differences among groups probably due to the small lesion size. Weconclude that increased GFAP+ higher complexity astrocytes areassociated with increased neuronal death and that NFkB pathway islikely to be involved in the pathological conversion to the pro-inflammatory-neurodegenerative phenotype.Fil: Cieri, M. B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Mailing, Ingrid Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaLXV Reunión anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Asociación Argentina de FisiologíaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Fisiologí