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

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

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