Neurogenesis Is Reduced at 48 h in the Subventricular Zone Independent of Cell Death in a Piglet Model of Perinatal Hypoxia-Ischemia

Cellular and tissue damage triggered after hypoxia-ischemia (HI) can be generalized and affect the neurogenic niches present in the central nervous system. As neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy, the goal of the present work was to investigate the neurogenic response to HI in the neurogenic niche of the subventricular zone (SVZ) in the neonatal piglet. A total of 13 large white male piglets aged <24 h were randomized into two groups: i) HI group (n = 7), animals submitted to transient cerebral HI and resuscitation; and ii) Control group (n = 6), non-HI animals. At 48 h, piglets were euthanized, and the SVZ and its surrounding regions, such as caudate and periventricular white matter, were analyzed for histology using hematoxylin-eosin staining and immunohistochemistry by evaluating the presence of cleaved caspase 3 and TUNEL positive cells, together with the cell proliferation/neurogenesis markers Ki67 (cell proliferation), GFAP (neural stem cells processes), Sox2 (neural stem/progenitor cells), and doublecortin (DCX, a marker of immature migrating neuroblasts). Hypoxic-ischemic piglets showed a decrease in cellularity in the SVZ independent of cell death, together with decreased length of neural stem cells processes, neuroblast chains area, DCX immunoreactivity, and lower number of Ki67 + and Ki67 + Sox2 + cells. These data suggest a reduction in both cell proliferation and neurogenesis in the SVZ of the neonatal piglet, which could in turn compromise the replacement of the lost neurons and the achievement of global repair.This work was supported by the United Kingdom Medical Research Council (G0501259), Basque Government Postdoctoral Program (POS_2013_1_191), EITB Maratoia- BIOEF (BIO18/IC/003), and the Spanish Ministry of Science and Innovation (MINECOR20/P66/AEI/10.13039/50110001103). This study was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the UK Department of Health’s National Institute for Health Research Biomedical Research Centers funding scheme

Punk Pioneers : Chicana Alice Bag as a Case in Point

This study aims to present Chicana punk musician Alice Bag as one of the main female figures who exerted a great influence on the early punk scene of Los Angeles, California, and thus helped to pave the way for a wider influx of female musicians within punk and to put some feminist issues at the forefront. By doing so, we will try to broaden the social and cultural understanding of punk music. Both Bag's autobiography Violence Girl, From East L.A. Rage to Hollywood Stage (2011) and her last LP, self-titled Alice Bag (2016), cover relevant issues related to Chicana women's condition, thus turning punk into a powerful platform to articulate feminist and ethnic concepts.El objetivo de este trabajo es presentar a la música chicana Alice Bag como una de las figuras influyentes en la temprana escena punk de Los Ángeles, California, quien ayudó a abrir el camino a una afluencia mayor de mujeres en la música punk, poniendo así algunos temas feministas en primera línea. De este modo, trataremos de ampliar el ámbito de estudio del punk. Tanto su autobiografía Violence Girl, From East L.A. Rage to Hollywood Stage (2011) y su casi recién estrenado LP Alice Bag (2016) abarcan temas relacionados con la condición de las mujeres chicanas, convirtiendo al punk en una poderosa plataforma de la que se ayuda para articular conceptos feministas y étnicos

Human histology. Manual of practicals

123 p.In Medicine, the samples use to come from patients from whom a portion of tissue is extracted, which is called a biopsy. They also come from material obtained by surgical treatment (surgical specimens) and, of course, from people who have died of some type of disease and whose family authorizes the autopsy to be performed (clinical autopsy). Many of the studies are carried out using extensions of exudates on slides, aspirated material or smears, which are generically known as cytology and/or extensions. The material must be obtained with great care, trying not to deform or damage the tissue: appropriate and sharp material must be used. The origin of the samples largely determines the “quality” of the material. It is extremely important that as little time as possible elapses between obtaining the sample and its fixation in order to have the highest degree of resemblance to the “in vivo” state. In the following, we will refer to the study methods most commonly used in daily practice

Bases moleculares del carcinoma endometrial. Invasión, diseminación y recurrencia

El carcinoma endometrial (CE) es el cáncer ginecológico más frecuente en los países desarrollados (Sankaranarayanan & Ferlay 2006) y representa la cuarta neoplasia en mujeres, después del cáncer de mama, pulmón y colon (Siegel et al. 2012). Normalmente se diagnostica en estadios tempranos, cuando la enfermedad está confinada en el útero, por lo que suele presentar un buen pronóstico. Sin embargo, en torno a un 20% de las pacientes presenta enfermedad avanzada al diagnóstico, lo que va asociado a un descenso en la supervivencia. En este contexto, el estudio de las células del tumor primario, con capacidad de invadir y colonizar localmente o a distancia, y de las células tumorales circulantes (CTC), fuente potencial de recurrencias, permitirá determinar nuevas dianas para controlar la aparición y desarrollo de metástasis. En nuestro estudio caracterizamos el programa transcripcional asociado a ETV5 en el frente de invasión de los carcinomas endometriales y determinamos la importancia de la regulación del factor neurotrófico BDNF. La sobreexpresión de ETV5 genera un fenotipo mesenquimal y un aumento en las capacidades de migración e invasión celular, a través de la participación del eje BDNF‐TrkBERK1/ 2. Además, el patrón de diseminación masivo que promueve ETV5 en un modelo in vivo, se revierte con el silenciamiento de BDNF. El fenotipo invasivo dirigido por ETV5 en el frente de invasión muestra una continuidad en el perfil molecular encontrado en las CTC de las pacientes con CE, a través de un patrón clásico de genes implicados en el proceso de transición epitelio‐mesénquima. La expresión de genes asociados con características de célula madre en las CTC sugiere potenciales dianas terapéuticas. Entre un 13‐17% de las mujeres con CE sufren una recurrencia, un tercio de ellas en regiones locales y dos tercios en lugares a distancia (Smith et al. 2007). En nuestro trabajo hemos identificado a ANXA2 como biomarcador de enfermedad recurrente demostrando su valor predictivo de recurrencia incluso en pacientes con carcinomas endometriales de bajo riesgo. La validación funcional de ANXA2 tanto in vitro como in vivo sugiere un papel principal en el proceso de diseminación y metástasis en el CE

Reformulando el movimiento Riot Grrrl: espacio y sororidad en las letras de Kathleen Hanna

La música se ha convertido en un espacio en el que debatir temas como el género, la iden- tidad o la igualdad. Con este trabajo pretendo llevar a cabo un análisis crítico del discurso con perspectiva feminista de las letras de canciones de Kathleen Hanna (1968-), cantante y compositora americana, pionera del movimiento punk y figura principal del movimiento Riot Grrrl. Cubriendo temas relevantes relacionados con la condición de las mujeres, las letras de Hanna sitúan temas relacionados con el género en primera línea y se convierten en un medio significativo para reclamar el feminismo en la música underground. Para mi estudio prestaré atención a las ocasiones en las que las letras de Hanna en Bikini Kill y Le Tigre muestran una interpretación del espacio y la sororidad y, con ello, analizaré la invisibilidad de las mujeres en la música underground y ampliaré el entendimiento social y cultural de la misma.Music has become a crucial domain to discuss issues such as gender, identities and equality. With this study I aim at carrying out a feminist critical discourse analysis of the lyrics by American singer and songwriter Kathleen Hanna (1968-), a pioneer within the underground punk culture and head figure of the Riot Grrrl movement. Covering relevant issues related to women’s conditions, Hanna’s lyrics put gender issues at the forefront and become a sig- nificant means to claim feminism in the underground. In this study I pay attention to the instances in which Hanna’s lyrics in Bikini Kill and Le Tigre exhibit a reading of sisterhood and space and by doing so, I will discuss women’s invisibility in underground music and broaden the social and cultural understanding of this music

Neonatal Brain Injury and the Search for New Therapies

DA-A was supported by EITB Maratoia-BIOEF (BIO18/IC/003) and the Spanish Ministry of Science and Innovation (MINECOR20/P66/AEI/10.13039/501100011033)

Neurogenesis Is Reduced at 48 h in the Subventricular Zone Independent of Cell Death in a Piglet Model of Perinatal Hypoxia-Ischemia

Cellular and tissue damage triggered after hypoxia-ischemia (HI) can be generalized and affect the neurogenic niches present in the central nervous system. As neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy, the goal of the present work was to investigate the neurogenic response to HI in the neurogenic niche of the subventricular zone (SVZ) in the neonatal piglet. A total of 13 large white male piglets aged <24 h were randomized into two groups: i) HI group (n = 7), animals submitted to transient cerebral HI and resuscitation; and ii) Control group (n = 6), non-HI animals. At 48 h, piglets were euthanized, and the SVZ and its surrounding regions, such as caudate and periventricular white matter, were analyzed for histology using hematoxylin-eosin staining and immunohistochemistry by evaluating the presence of cleaved caspase 3 and TUNEL positive cells, together with the cell proliferation/neurogenesis markers Ki67 (cell proliferation), GFAP (neural stem cells processes), Sox2 (neural stem/progenitor cells), and doublecortin (DCX, a marker of immature migrating neuroblasts). Hypoxic-ischemic piglets showed a decrease in cellularity in the SVZ independent of cell death, together with decreased length of neural stem cells processes, neuroblast chains area, DCX immunoreactivity, and lower number of Ki67 + and Ki67 + Sox2 + cells. These data suggest a reduction in both cell proliferation and neurogenesis in the SVZ of the neonatal piglet, which could in turn compromise the replacement of the lost neurons and the achievement of global repair

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade

Therapeutic hypothermia modulates the neurogenic response of the newborn piglet subventricular zone after hypoxia-ischemia

BACKGROUND: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. To investigate the neurogenic response to hypoxia-ischemia (HI) followed by normothermia (38.5 °C) or three different hypothermic temperatures (35, 33.5, or 30 °C) in the subventricular zone (SVZ) of the neonatal piglet. METHODS: Following transient cerebral HI and resuscitation, 28 newborn piglets were randomized to: normothermia or whole-body cooling to 35 °C, 33.5 °C, or 30 °C during 2-26 h (all n = 7). At 48 h, piglets were euthanized and SVZ obtained to evaluate its cellularity, pattern of cell death, radial glia length, doublecortin (DCX, neuroblasts) expression, and Ki67 (cell proliferation) and Ki67/Sox2 (neural stem/progenitor dividing) cell counts. RESULTS: Normothermic piglets showed lower total (Ki67+) and neural stem/progenitor dividing (Ki67+Sox2+) cell counts when compared to hypothermic groups. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and DCX immunohistochemistry. Cooling to 30 °C, however, revealed decreased cellularity in the lateral SVZ and shorter radial glia processes when compared with 33.5 °C. CONCLUSIONS: In a neonatal piglet model, hypothermia to 33.5 °C modulates the neurogenic response of the SVZ after HI, highlighting the potential beneficial effect of hypothermia to 33.5 °C on endogenous neurogenesis and the detrimental effect of overcooling beyond this threshold. IMPACT: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. Hypothermia may modulate neurogenesis in the subventricular zone (SVZ) of the neonatal hypoxic-ischemic piglet. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and doublecortin immunohistochemistry; cooling to 30 °C, however, revealed decreased cellularity and shorter radial glia processes. In a neonatal piglet model, therapeutic hypothermia (33.5 °C) modulates the neurogenic response of the SVZ after hypoxia-ischemia, highlighting also the detrimental effect of overcooling beyond this threshold