Microelectrode arrays in combination with in vitro models of spinal cord injury as tools to investigate pathological changes in network activity: facts and promises

Microelectrode arrays (MEAs) represent an important tool to study the basic characteristics of spinal networks that control locomotion in physiological conditions. Fundamental properties of this neuronal rhythmicity like burst origin, propagation, coordination and resilience can, thus, be investigated at multiple sites within a certain spinal topography and neighbouring circuits. A novel challenge will be to apply this technology to unveil the mechanisms underlying pathological processes evoked by spinal cord injury. To achieve this goal, it is necessary to fully identify spinal networks that make up the locomotor central pattern generator (CPG) and to understand their operational rules. In this review, the use of isolated spinal cord preparations from rodents, or organotypic spinal slice cultures is discussed to study rhythmic activity. In particular, this review surveys our recently developed in vitro models of spinal cord injury by evoking excitotoxic (or even hypoxic/dysmetabolic) damage to spinal networks and assessing their impact on rhythmic activity and cell survival. These pathological processes which evolve via different cell death mechanisms are discussed as a paradigm to apply MEA recording for detailed mapping of the functional damage and its time-dependent evolution. \ua9 2013 Mladinic and Nistri

The differential intracellular expression of the novel marker ATF-3 characterizes the quiescent or activated state of endogenous spinal stem cells: a tool to study neurorepair?

Worldwide, spinal cord injury (SCI) remains a major cause of disability with serious consequences in terms of personal and social costs [1]. Thus, important issues are how to protect the spinal cord to limit its initial damage, how to repair a lesion, and how to facilitate recovery by exploiting surviving tissue. These needs are currently unmet because our knowledge of the detailed structure of the neuronal networks responsible for human locomotion is scanty and our control over the mechanisms involved in neuronal death and regeneration is very limited. The molecular mechanisms underlying neuronal death after SCI are incompletely understood so that specific strategies for neuroprotection remain preliminary [2-4]. While many neuroprotective molecules have been reported to be experimentally effective for neuronal survival after SCI, very few have reached the clinical testing stage and none of them has provided efficacious treatment for SCI patients [5]. The reasons for such a clinical failure are complex and may include the diversity of protocols used to induce injury in animal models and the difficulty of detailed animal tissue analysis beyond a single time point so that a relatively narrow window of pathophysiology may be explored [6,7]. In clinical settings, the large majority of SCI cases are managed at late stages after the patient\u2019s conditions have been stabilized following the primary lesion. Hence, damage repair rather than neuroprotection becomes a crucial goal

Mechanisms underlying cell death in ischemia-like damage to the rat spinal cord in vitro

New spinal cord injury (SCI) cases are frequently due to non-traumatic causes, including vascular disorders. To develop mechanism-based neuroprotective strategies for acute SCI requires full understanding of the early pathophysiological changes to prevent disability and paralysis. The aim of our study was to identify the molecular and cellular mechanisms of cell death triggered by a pathological medium (PM) mimicking ischemia in the rat spinal cord in vitro. We previously showed that extracellular Mg2+ (1 mM) worsened PM-induced damage and inhibited locomotor function. The present study indicated that 1 h of PM+Mg2+ application induced delayed pyknosis chiefly in the spinal white matter via overactivation of poly (ADP-ribose) polymerase 1 (PARP1), suggesting cell death mediated by the process of parthanatos that was largely suppressed by pharmacological block of PARP-1. Gray matter damage was less intense and concentrated in dorsal horn neurons and motoneurons that became immunoreactive for the mitochondrial apoptosis-inducing factor (the intracellular effector of parthanatos) translocated into the nucleus to induce chromatin condensation and DNA fragmentation. Immunoreactivity to TRPM ion channels believed to be involved in ischemic brain damage was also investigated. TRPM2 channel expression was enhanced 24 h later in dorsal horn and motoneurons, whereas TRPM7 channel expression concomitantly decreased. Conversely, TRPM7 expression was found earlier (3 h) in white matter cells, whereas TRPM2 remained undetectable. Simulating acute ischemic-like damage in vitro in the presence of Mg2+ showed how, during the first 24 h, this divalent cation unveiled differential vulnerability of white matter cells and motoneurons, with distinct changes in their TRPM expression. \ua9 2013 Macmillan Publishers Limited All rights reserved

El trauma raquimedular

A medula espinhal dos mamíferos adultos não permite a regeneração de axônios. Por razões ainda desconhecidas, as fibras neurais falham em cruzar o sítio da lesão, como se não houvesse crescimento, desde a primeira tentativa. Quais mecanismos poderiam explicar a perda da capacidade de regeneração? As cicatrizes formadas pelas células da glia seriam uma consequência da falha na regeneração ou a causa? Diversas linhas de evidência sugerem que a regeneração da medula espinhal seria impedida no sistema nervoso central pela ação de fatores locais no sítio da lesão, e que o sistema nervoso central não-lesado é um meio permissivo para o crescimento axonal, na direção de alvos específicos. Uma vez que os axônios são induzidos adequadamente a cruzar a lesão com o auxílio de implantes, fármacos ou células indiferenciadas, as fibras em regeneração podem encontrar a via específica e estabelecer conexões corretas. O que ainda não se sabe é que combinação de moléculas induz/inibe o potencial de regeneração do tecido e que mecanismos permitem aos neurônios formarem conexões específicas com os alvos com os quais são programados a fazer.The adult mammal spinal cord does not allow axons regeneration. For unknown reasons, the neural fibers fail in coming across the site of the lesion, as if there were no growing from the first try. What mechanisms may explain the lost of regeneration capability? Are scars formed by glial cells a consequence of regeneration fail or the cause? Several evidence lines suggest that spinal cord regeneration would be blocked in the central nervous system by actions of local factors in the site of the wound, and no injured central nervous system is a permissive way for the axonal growing into specific targets. If axons are correctly induced to cross the injury, supported by implants, drugs and undifferentiated cells, the fibers in regeneration may find a specific way to establish the right connections. The combination of molecules which induce/inhibit the regeneration potential of the tissue remains unknown, as well as the mechanisms that enable the neuron to make specific connections with targets it is programmed to connect with.La medula espinal de los mamíferos adultos no permite la regeneración de los axones. Por razones aun no conocidas, las fibras neurales fallan en la tarea de cruzar por el sitio de la lesión, como si no hubiese crecimiento, desde el primer intento. ¿Cuáles mecanismos podrían explicar la pérdida de la capacidad de la regeneración? ¿Las cicatrices formadas por las células de la glía son una consecuencia del fallo en la regeneración o serían la causa? Diversas líneas de evidencia sugieren que la regeneración de la medula espinal sería impedida en el sistema nervioso central por la acción de factores locales en el sitio de la lesión, y que el sistema nervioso central no lesionado es un medio permisivo para el crecimiento axonal, en la dirección de dianas específicas. Una vez que los axones sean inducidos adecuadamente a cruzar la lesión, con auxilio de implantes, fármacos o células indiferenciadas, las fibras en regeneración podrían encontrar la vía específica y establecer conexiones correctas. Lo que aun es desconocido es que combinación de moléculas induce/inhibe el potencial de regeneración del tejido y cuáles mecanismos permiten a las neuronas formar conexiones específicas, con las dianas que son programadas a hacer.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

Фрагменти до біографії І. Мазепи

Мета цієї статті увести до наукового обігу три документи, які стосуються життя й діяльності І. Мазепи. Перший з них нами було виявлено у польських архівосховищах. Автором цього листа, адресованого, очевидно, королеві Яну III Собеському, був учасник посольства Речі Посполитої до Москви, яке очолював вармінський біскуп і коронний канцлер Августин Міхал Радзейовський. Лист важливий тим, що проливає світло на малознаний період біографії Івана Мазепи, коли той був генеральним осавулом на лівобічній Гетьманщині. Другий і третій документи мають меншу цінність. Один з них - це типова рукописна газета - “новина”, у якій повідомляється про польсько-російські переговори у Варшаві у 1695 р. у зв’язку з азово-дніпровськими походами, у котрих визначну роль відіграли українські війська на чолі з гетьманом Іваном Мазепою. Автором наступного документа був Лаврентій Крщонович, визначний церковний діяч, ігумен деяких православних монастирів Гетьманщини, зокрема Свято-Троїцького Іллінського у Чернігові

Beyond Prejudice as Simple Antipathy: Hostile and Benevolent Sexism Across Cultures

The authors argue that complementary hostile and benevolent componen:s of sexism exist ac ro.ss cultures. Male dominance creates hostile sexism (HS). but men's dependence on women fosters benevolent sexism (BS)-subjectively positive attitudes that put women on a pedestal but reinforce their subordination. Research with 15,000 men and women in 19 nations showed that (a) HS and BS are coherenl constructs th at correlate positively across nations, but (b) HS predicts the ascription of negative and BS the ascription of positive traits to women, (c) relative to men, women are more likely to reject HS than BS. especially when overall levels of sexism in a culture are high, and (d) national averages on BS and HS predict gender inequal ity across nations. These results challenge prevailing notions of prejudice as an antipathy in that BS (an affectionate, patronizing ideology) reflects inequality and is a cross-culturally pervasive complement to HS

International Perspectives on the Legal Environment for Selection

Perspectives from 22 countries on aspects of the legal environment for selection are presented in this article. Issues addressed include (a) whether there are racial/ethnic/religious subgroups viewed as "disadvantaged,” (b) whether research documents mean differences between groups on individual difference measures relevant to job performance, (c) whether there are laws prohibiting discrimination against specific groups, (d) the evidence required to make and refute a claim of discrimination, (e) the consequences of violation of the laws, (f) whether particular selection methods are limited or banned, (g) whether preferential treatment of members of disadvantaged groups is permitted, and (h) whether the practice of industrial and organizational psychology has been affected by the legal environmen

Apertura al Exterior y Negociaciones Comerciales. Lecciones y Experiencias del Caso Chileno

100 páginas. Serie Publicaciones Misceláneas.EL presente texto recoge lecciones de la experiencia chilena presentados por un actor directamente involucrado en las decisiones comerciales y negociación de la integración de Chile a MERCOSUR