Quantitative Kinematic Characterization of Reaching Impairments in Mice After a Stroke

Background and Objective. Kinematic analysis of reaching movements is increasingly used to evaluate upper extremity function after cerebrovascular insults in humans and has also been applied to rodent models. Such analyses can require time-consuming frame-by-frame inspections and are affected by the experimenter's bias. In this study, we introduce a semi-automated algorithm for tracking forepaw movements in mice. This methodology allows us to calculate several kinematic measures for the quantitative assessment of performance in a skilled reaching task before and after a focal cortical stroke. Methods. Mice were trained to reach for food pellets with their preferred paw until asymptotic performance was achieved. Photothrombosis was then applied to induce a focal ischemic injury in the motor cortex, contralateral to the trained limb. Mice were tested again once a week for 30 days. A high frame rate camera was used to record the movements of the paw, which was painted with a nontoxic dye. An algorithm was then applied off-line to track the trajectories and to compute kinematic measures for motor performance evaluation. Results. The tracking algorithm proved to be fast, accurate, and robust. A number of kinematic measures were identified as sensitive indicators of poststroke modifications. Based on end-point measures, ischemic mice appeared to improve their motor performance after 2 weeks. However, kinematic analysis revealed the persistence of specific trajectory adjustments up to 30 days poststroke, indicating the use of compensatory strategies. Conclusions. These results support the use of kinematic analysis in mice as a tool for both detection of poststroke functional impairments and tracking of motor improvements following rehabilitation. Similar studies could be performed in parallel with human studies to exploit the translational value of this skilled reaching analysis

Pharmacological rescue of adult hippocampal neurogenesis in a mouse model of X-linked intellectual disability

Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophnl affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophnl display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CM, and showed an altered density of dendritic protrusions. Since Ophnl-deficient mice display overactivation of Rho-associated protein kinase (ROCK) and protein kinase A (PICA) signaling, we administered a clinically approved ROCK/PICA inhibitor (fasudil) to correct the neurogenesis defects. While administration of fasudil was not effective in rescuing axon formation, the same treatment completely restored spine density to control levels, and enhanced the long-term survival of adult-born neurons in mice lacking Ophn1. These results identify specific neurodevelopmental steps that are impacted by Ophn1 deletion, and indicate that they may be at least partially corrected by pharmacological treatment. (C) 2017 The Authors. Published by Elsevier Inc

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration

U-Pb geochronology and paleogeography of the Valanginian–Hauterivian Neuquén Basin: Implications for Gondwana-scale source areas

Sedimentary basins located at the margins of continents act as the final base level for continental-scale catchments that are sometimes located thousands of kilometers away from the basin, and this condition of exceptionally long sediment transfer zones is probably reinforced in supercontinents, such as Gondwana. One of the most prominent marine basins in southwestern Gondwana during the Jurassic and Early Cretaceous was the Neuquén Basin (west-central Argentina), but its role as a sediment repository of far-flung source areas has not been extensively considered. This contribution provides the first detailed detrital-zircon U-Pb geochronology of the Valanginian–Hauterivian Pilmatué Member of the Agrio Formation, which is combined with sedimentology and paleogeographic reconstructions of the unit within the Neuquén Basin for a better understanding of the fluvial delivery systems. Our detrital-zircon signatures suggest that Triassic–Permian zircon populations were probably sourced from the adjacent western sector of the North Patagonian Massif, whereas Early Jurassic, Cambrian, Ordovician, and Proterozoic grains were most likely derived from farther east, in the eastern sector of the North Patagonian Massif, as well as presently remote terranes such as the Saldania Belt in southern Africa. We thus propose a Valanginian–Hauterivian longitudinal delivery system that, starting in the mid-continent region of southwestern Gondwana and by effective sorting, was bringing fine-grained or finer caliber sand to the Neuquén Basin shoreline. This delivery system was probably active (though not necessarily continuously) from Early Jurassic to Early Cretaceous until finally coming to an end during the opening of the South Atlantic Ocean in the latest Early Cretaceous.Fil: Schwarz, Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Finzel, E.S.. University of Iowa; Estados UnidosFil: Veiga, Gonzalo Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Rapela, Carlos Washington. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Echevarria, C.. No especifíca;Fil: Spalletti, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; Argentin

Composición normativa y clasificación de rocas pelíticas

A normative classification oi pelitic rocks based on the proportion of major components (SiO" AI,O" Fe,O" MgO, Cao, Na,O, K,O, P,O. and CO,) is presented in this paper. The proposecl procedure includes two models of norm calculation: smectite present and smectite absent. In hoth models the content of K,O can he lIsed to determina te orthoclase  illite. The pelitic rack classificationis based upon the relative contentsin normative clay minerals,quartz and feldspars. Nine compositionalrock-types,which are clearlydefined in a triangulardiagramwere recognized. The importance of chemical compositionstudies in the interpretation of pelitic rocksis also discussed.Se da a conocer un método normativo de clasificación de rocas pelíticas basado en su composición química mayoritaria (SiO" ALO" Fe-..O",MgO, CaO, Na,O, K:O, P,O. y CO,). El procedimiento propuesto presenta dos modelos de norma, con o sin esmectita. En ambos modelos los contenjclos de K,O pueden ser asignados a Oltosa o a illita. La clasificación de las pelitas está basada en las proporciones normativas de argilominerales, cuarzo y fesdespatos. En ella se reconocen nueve variedades composicionales, las que se pueden representar en un diagrama triangular. Se discute el valor de los estudios qlÚmicos composicionales en la interpret'1ción genética de sucesiones y rocas pelíticas

Análisis morfológico del Río Pilcomayo en la zona de la embocadura

La zona de la Embocadura en el Río Pilcomayo, se corresponde con una bifurcación del mismo que reparte las aguas hacia Argentina y Paraguay. Se localiza en el extremo noroeste de la provincia de Formosa, Argentina. Este sector del Río Pilcomayo presenta una marcada inestabilidad desde el punto de vista morfológico. A pesar de ello, la necesidad de captar agua del río por parte de Argentina y Paraguay, ha motivado la realización de una serie de intervenciones en esta zona durante los últimos 25 años. En la actualidad existen convenios entre ambos países de los que surge el compromiso de realizar acciones coordinadas tendientes a lograr un reparto equitativo de las aguas y los sedimentos.La finalidad de este estudio es hacer una evaluación de los cambios que la planta del cauce experimentó en los últimos tiempos, y ubicar sectores que eventualmente puedan tener una mayor estabilidad. En principio, las obras de repartición debieran localizarse en estos sitios para que puedan cumplir con los compromisos de ambos países de manera estable en el tiempo.Fil: Irigoyen, M. Instituto Nacional del Agua; Argentina.Fil: Irigoyen, M. Universidad Nacional de La Plata. Facultad de Ingeniería; Argentina.Fil: Spalletti, P. Instituto Nacional del Agua; Argentina.Fil: Spalletti, P. Universidad Nacional de La Plata. Facultad de Ingeniería; Argentina.Fil: Brea, D. Instituto Nacional del Agua; Argentina.Fil: Brea, D. Universidad Nacional de La Plata. Facultad de Ingeniería; Argentina.Fil: Hillman, G. Universidad Nacional de Córdoba. Facultad de Ingeniería. Laboratorio de Hidráulica; Argentina.Fil: Gyssels, P. Universidad Nacional de Córdoba. Facultad de Ingeniería. Laboratorio de Hidráulica; Argentina.Fil: Baldissone, C. Instituto Nacional del Agua; Argentina.Fil: Rodríguez, A. Universidad Nacional de Córdoba. Facultad de Ingeniería. Laboratorio de Hidráulica; Argentina.Ingeniería Civi

U-Pb geochronology and paleogeography of the Valanginian–Hauterivian Neuquén Basin: Implications for Gondwana-scale source areas

Sedimentary basins located at the margins of continents act as the final base level for con­tinental-scale catchments that are sometimes located thousands of kilometers away from the basin, and this condition of exceptionally long sediment transfer zones is probably reinforced in supercontinents, such as Gondwana. One of the most prominent marine basins in southwestern Gondwana during the Jurassic and Early Cretaceous was the Neuquén Basin (west-central Argentina), but its role as a sediment repository of far-flung source areas has not been extensively considered. This contribution provides the first detailed detrital-zircon U-Pb geochronology of the Valanginian–Hauterivian Pilmatué Member of the Agrio Formation, which is combined with sedimentology and paleogeographic reconstructions of the unit within the Neuquén Basin for a better understanding of the fluvial delivery systems. Our detrital-zircon signatures suggest that Triassic–Permian zircon populations were probably sourced from the adjacent western sector of the North Patagonian Massif, whereas Early Jurassic, Cambrian, Ordovician, and Proterozoic grains were most likely derived from farther east, in the eastern sector of the North Patagonian Massif, as well as presently remote terranes such as the Saldania Belt in southern Africa. We thus propose a Valanginian–Hauterivian longitudinal delivery system that, starting in the mid-continent region of southwestern Gondwana and by effective sorting, was bringing fine-grained or finer caliber sand to the Neuquén Basin shoreline. This delivery system was probably active (though not necessarily continuously) from Early Jurassic to Early Cretaceous until finally coming to an end during the opening of the South Atlantic Ocean in the latest Early Cretaceous.Centro de Investigaciones Geológica

Obese mice exposed to psychosocial stress display cardiac and hippocampal dysfunction associated with local brain-derived neurotrophic factor depletion

Introduction: Obesity and psychosocial stress (PS) co-exist in individuals of Western society. Nevertheless, how PS impacts cardiac and hippocampal phenotype in obese subjects is still unknown. Nor is it clear whether changes in local brain-derived neurotrophic factor (BDNF) account, at least in part, for myocardial and behavioral abnormalities in obese experiencing PS. Methods: In adult male WT mice, obesity was induced via a high-fat diet (HFD). The resident-intruder paradigm was superimposed to trigger PS. In vivo left ventricular (LV) performance was evaluated by echocardiography and pressure-volume loops. Behaviour was indagated by elevated plus maze (EPM) and Y-maze. LV myocardium was assayed for apoptosis, fibrosis, vessel density and oxidative stress. Hippocampus was analyzed for volume, neurogenesis, GABAergic markers and astrogliosis. Cardiac and hippocampal BDNF and TrkB levels were measured by ELISA and WB. We investigated the pathogenetic role played by BDNF signaling in additional cardiac-selective TrkB (cTrkB) KO mice. Findings: When combined, obesity and PS jeopardized LV performance, causing prominent apoptosis, fibrosis, oxidative stress and remodeling of the larger coronary branches, along with lower BDNF and TrkB levels. HFD/PS weakened LV function similarly in WT and cTrkB KO mice. The latter exhibited elevated LV ROS emission already at baseline. Obesity/PS augmented anxiety-like behaviour and impaired spatial memory. These changes were coupled to reduced hippocampal volume, neurogenesis, local BDNF and TrkB content and augmented astrogliosis. Interpretation: PS and obesity synergistically deteriorate myocardial structure and function by depleting cardiac BDNF/TrkB content, leading to augmented oxidative stress. This comorbidity triggers behavioral deficits and induces hippocampal remodeling, potentially via lower BDNF and TrkB levels. Fund: J.A. was in part supported by Rotary Foundation Global Study Scholarship. G.K. was supported by T32 National Institute of Health (NIH) training grant under award number 1T32AG058527. S.C. was funded by American Heart Association Career Development Award (19CDA34760185). G.A.R.C. was funded by NIH (K01HL133368-01). APB was funded by a Grant from the Friuli Venezia Giulia Region entitled: “Heart failure as the Alzheimer disease of the heart; therapeutic and diagnostic opportunities”. M.C. was supported by PRONAT project (CNR). N.P. was funded by NIH (R01 HL136918) and by the Magic-That-Matters fund (JHU). V.L. was in part supported by institutional funds from Scuola Superiore Sant'Anna (Pisa, Italy), by the TIM-Telecom Italia (WHITE Lab, Pisa, Italy), by a research grant from Pastificio Attilio Mastromauro Granoro s.r.l. (Corato, Italy) and in part by ETHERNA project (Prog. n. 161/16, Fondazione Pisa, Italy). Funding source had no such involvement in study design, in the collection, analysis, interpretation of data, in the writing of the report; and in the decision to submit the paper for publication

Neurophysiological and neuroradiological test for early poor outcome (Cerebral Performance Categories 3\u20135) prediction after cardiac arrest: Prospective multicentre prognostication data

The data presented here are related to our research article entitled \u201cNeurophysiology and neuroimaging accurately predict poor neurological outcome within 24 hours after cardiac arrest: a prospective multicentre prognostication study (ProNeCA)\u201d [1]. We report a secondary analysis on the ability of somatosensory evoked potentials (SEPs), brain computed tomography (CT) and electroencephalography (EEG) to predict poor neurological outcome at 6 months in 346 patients who were comatose after cardiac arrest. Differently from the related research article, here we included cerebral performance category (CPC) 3 among poor outcomes, so that the outcomes are dichotomised as CPC 1\u20132 (absent to mild neurological disability: good outcome) vs. CPC 3\u20135 (severe neurological disability, persistent vegetative state, or death: poor outcome). The accuracy of the index tests was recalculated accordingly. A bilaterally absent/absent-pathological amplitude (AA/AP) N20 SEPs wave, a Grey Matter/White Matter (GM/WM) ratio <1.21 on brain CT and an isoelectric or burst suppression EEG predicted poor outcome with 49.6%, 42.2% and 29.8% sensitivity, respectively, and 100% specificity. The distribution of positive results of the three predictors did not overlap completely in the population of patients with poor outcome, so that when combining them the overall sensitivity raised to 61.2%