RESUMO
Importance: Deviations from international resuscitation guidelines during the management of pediatric cardiac arrest are frequent and affect clinical outcomes. An interactive tablet application (app), PediAppRREST, was developed to reduce guideline deviations during pediatric cardiac arrest. Objective: To assess the effectiveness of PediAppRREST in improving the management of simulated in-hospital pediatric cardiac arrest. Design, Setting, and Participants: This multicenter 3-group simulation-based randomized clinical trial was conducted from September 2020 to December 2021 at 4 Italian university hospitals (Padua, Florence, Rome, Novara). Participants included residents in pediatrics, emergency medicine, and anesthesiology. Analyses were conducted as intention-to-treat. Data were analyzed from January to June 2022. Interventions: Teams were randomized to 1 of 3 study groups: an intervention group that used the PediAppRREST app; a control group that used a paper-based cognitive aid, the Pediatric Advanced Life Support (PALS) pocket card; and a control group that used no cognitive aids. All the teams managed the same standardized simulated scenario of nonshockable pediatric cardiac arrest. Main Outcomes and Measures: The primary outcome was the number of deviations from guidelines, measured by a 15-item checklist based on guideline recommendations. The main secondary outcomes were quality of chest compressions, team clinical performance (measured by the Clinical Performance Tool), and perceived team leader's workload. Study outcomes were assessed via video reviews of the scenarios. Results: Overall 100 teams of 300 participants (mean [SD] age, 29.0 [2.2] years; 195 [65%] female) were analyzed by intention-to-treat, including 32 teams randomized to the PediAppRREST group, 35 teams randomized to the PALS control group, and 33 teams randomized to the null control group. Participant characteristics (210 pediatric residents [70%]; 48 anesthesiology residents [16%]; 42 emergency medicine residents [14%]) were not statistically different among the study groups. The number of deviations from guidelines was significantly lower in the PediAppRREST group than in the control groups (mean difference vs PALS control, -3.0; 95% CI, -4.0 to -1.9; P < .001; mean difference vs null control, -2.6; 95% CI, -3.6 to -1.5; P < .001). Clinical Performance Tool scores were significantly higher in the PediAppRREST group than control groups (mean difference vs PALS control, 1.4; 95% CI, 0.4 to 2.3; P = .002; mean difference vs null control, 1.1; 95% CI, 0.2 to 2.1; P = .01). The other secondary outcomes did not significantly differ among the study groups. Conclusions and Relevance: In this randomized clinical trial, the use of the PediAppRREST app resulted in fewer deviations from guidelines and a better team clinical performance during the management of pediatric cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT04619498.
Assuntos
Anestesiologia , Parada Cardíaca , Humanos , Criança , Feminino , Adulto , Masculino , Parada Cardíaca/terapia , Ressuscitação , BiometriaRESUMO
INTRODUCTION: Chemical-biological-radiological-nuclear-explosive (CBRNe) are complex events. Decontamination is mandatory to avoid harm and contain hazardous materials, but can delay care. Therefore, the stabilization of patients in the warm zone seems reasonable, but research is limited. Moreover, subjects involved in biological events are considered infectious even after decontamination and need to be managed while wearing personal protective equipment (PPE), as seen with Ebola and COVID-19 pandemic. With this simulation mannequin trial, we assessed the impact of CBRNe PPE on cardiopulmonary resuscitation and combat casualty care procedures. METHODS: We compared procedures performed by emergency medicine and anesthesiology senior residents, randomized in 2 groups (CBRNe PPE vs. no PPE). Chest compression (CC) depth was defined as the primary outcome. Time to completion was calculated for the following: tourniquet application; tension pneumothorax needle decompression; peripheral venous access (PVA) and intraosseous access positioning; and drug preparation and administration. A questionnaire was delivered to evaluate participants' perception. RESULTS: Thirty-six residents participated. No significant difference between the groups in CC depth (mean difference = 0.26 cm [95% confidence interval = -0.26 to 0.77 cm, P = 0.318]), as well as for CC rate, CC complete release, and time for drugs preparation and administration was detected. The PPE contributed to significantly higher times for tourniquet application, tension pneumothorax decompression, peripheral venous access, and intraosseous access positioning. The residents found simulation relevant to the residencies' core curriculum. CONCLUSIONS: This study suggests that cardiopulmonary resuscitation can be performed while wearing PPE without impacting quality, whereas other tasks requiring higher dexterity can be significantly impaired by PPE.Trial Registration Number: NCT04367454, April 29, 2020 (retrospectively registered).
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COVID-19 , Equipamento de Proteção Individual , Humanos , Manequins , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. RESULTS: In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24-March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. CONCLUSIONS: Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.
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Anestesia/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Desflurano/efeitos adversos , Obesidade Mórbida/complicações , Anestesia/métodos , Anestésicos Inalatórios/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Desflurano/administração & dosagem , Feminino , Gastroplastia/efeitos adversos , Gastroplastia/métodos , Glucocorticoides/uso terapêutico , Humanos , Testes de Função Hepática , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Resultado do TratamentoRESUMO
Synaptodendritic pruning and alterations in neurotransmission are the main underlying causes of HIV-associated neurocognitive disorders (HAND). Our studies in humans and nonhuman primates indicated that the protein ferritin heavy chain (FHC) is a critical player in neuronal changes and ensuing cognitive deficit observed in these patients. Here we focus on the effect of HIV proteins and inflammatory cytokines implicated in HAND on neuronal FHC levels, dendritic changes, and neurocognitive behavior. In two well characterized models of HAND (HIV transgenic and gp120-treated rats), we report reductions in spine density and dendritic branches in prefrontal cortex pyramidal neurons compared with age-matched controls. FHC brain levels are elevated in these animals, which also show deficits in reversal learning. Moreover, IL-1ß, TNF-α, and HIV gp120 upregulate FHC in rat cortical neurons. However, although the inflammatory cytokines directly altered neuronal FHC, gp120 only caused significant FHC upregulation in neuronal/glial cocultures, suggesting that glia are necessary for sustained elevation of neuronal FHC by the viral protein. Although the envelope protein induced secretion of IL-1ß and TNF-α in cocultures, TNF-α blockade did not affect gp120-mediated induction of FHC. Conversely, studies with an IL-1ß neutralizing antibody or specific IL-1 receptor antagonist revealed the primary involvement of IL-1ß in gp120-induced FHC changes. Furthermore, silencing of neuronal FHC abrogates the effect of gp120 on spines, and spine density correlates negatively with FHC levels or cognitive deficit. These results demonstrate that viral and host components of HIV infection increase brain expression of FHC, leading to cellular and functional changes, and point to IL-1ß-targeted strategies for prevention of these alterations. Significance statement: This work demonstrates the key role of the cytokine IL-1ß in the regulation of a novel intracellular mediator [i.e., the protein ferritin heavy chain (FHC)] of HIV-induced dendritic damage and the resulting neurocognitive impairment. This is also the first study that systematically investigates dendritic damage in layer II/III prefrontal cortex neurons of two different non-infectious models of HIV-associated neurocognitive disorders (HAND) and reveals a precise correlation of these structural changes with specific biochemical and functional alterations also reported in HIV patients. Overall, these data suggest that targeting the IL-1ß-dependent FHC increase may represent a valid strategy for neuroprotective adjuvant therapies in HAND.
Assuntos
Complexo AIDS Demência/patologia , Apoferritinas/metabolismo , Interleucina-1beta/metabolismo , Neurônios/patologia , Complexo AIDS Demência/metabolismo , Animais , Western Blotting , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , HIV-1 , Imuno-Histoquímica , Neurônios/metabolismo , Ratos , Ratos Transgênicos , Proteínas Virais/metabolismoRESUMO
Interaction of the chemokine CXCL12 with its receptor CXCR4 promotes neuronal function and survival during embryonic development and throughout adulthood. Previous studies indicated that µ-opioid agonists specifically elevate neuronal levels of the protein ferritin heavy chain (FHC), which negatively regulates CXCR4 signaling and affects the neuroprotective function of the CXCL12/CXCR4 axis. Here, we determined that CXCL12/CXCR4 activity increased dendritic spine density, and also examined FHC expression and CXCR4 status in opiate abusers and patients with HIV-associated neurocognitive disorders (HAND), which is typically exacerbated by illicit drug use. Drug abusers and HIV patients with HAND had increased levels of FHC, which correlated with reduced CXCR4 activation, within cortical neurons. We confirmed these findings in a nonhuman primate model of SIV infection with morphine administration. Transfection of a CXCR4-expressing human cell line with an iron-deficient FHC mutant confirmed that increased FHC expression deregulated CXCR4 signaling and that this function of FHC was independent of iron binding. Furthermore, examination of morphine-treated rodents and isolated neurons expressing FHC shRNA revealed that FHC contributed to morphine-induced dendritic spine loss. Together, these data implicate FHC-dependent deregulation of CXCL12/CXCR4 as a contributing factor to cognitive dysfunction in neuroAIDS.
Assuntos
Complexo AIDS Demência/complicações , Apoferritinas/química , Neurônios/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/complicações , Complexo AIDS Demência/fisiopatologia , Adulto , Idoso , Animais , Encéfalo/efeitos dos fármacos , Linhagem Celular , Quimiocina CXCL12/metabolismo , Espinhas Dendríticas/efeitos dos fármacos , Feminino , Humanos , Ferro/química , Macaca , Masculino , Pessoa de Meia-Idade , Morfina/química , Neurônios/metabolismo , Técnicas de Patch-Clamp , Fosforilação , RNA Interferente Pequeno/metabolismo , Ratos , Receptores CXCR4/metabolismo , Transtornos Relacionados ao Uso de Substâncias/fisiopatologiaRESUMO
Evidence indicates that the degeneration of basal forebrain cholinergic neurons may represent an important factor underlying the progressive cognitive decline characterizing Alzheimer's disease (AD). However, the nature of the relationship between cholinergic depletion and AD is not fully elucidated. This study aimed at clarifying some aspects of the relation existing between deficits in cerebral energy metabolism and degeneration of cholinergic system in AD, by investigating the neuronal metabolic activity of several cortical areas after depletion of basal forebrain cholinergic neurons. In cholinergically depleted rats, we evaluated the neuronal metabolic activity by assaying cytochrome oxidase (CO) activity in frontal, parietal and posterior parietal cortices at four different time-points after unilateral injection of 192 IgG-saporin in the nucleus basalis magnocellularis. Unilateral depletion of cholinergic cells in the basal forebrain induced a bilateral decrease of metabolic activity in all the analyzed areas. Frontal and parietal cortices showed decreased metabolic activity even 3 days after the lesion, when the cholinergic degeneration was still incomplete. In posterior parietal cortex metabolic activity decreased only 7 days after the lesion. The possible molecular mechanisms underlying these findings were also investigated. Real-time PCR showed an increase of CO mRNA levels at 3, 7 and 15 days after the lesion both in frontal and parietal cortices, followed by normalization at 30 days. Western Blot analysis did not show any change in CO protein levels at any time-point after the lesion. Our findings support a link between metabolic deficit and cholinergic hypofunctionality characterizing AD pathology. The present model of cholinergic hypofunctionality provides a useful means to study the complex mechanisms linking two fundamental and interrelated phenomena characterizing AD from the early stages.
Assuntos
Córtex Cerebral/metabolismo , Neurônios Colinérgicos/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Degeneração Neural/fisiopatologia , Prosencéfalo/fisiopatologia , Doença de Alzheimer/patologia , Animais , Anticorpos Monoclonais , Núcleo Basal de Meynert , Córtex Cerebral/patologia , Complexo IV da Cadeia de Transporte de Elétrons/biossíntese , Masculino , Ratos , Ratos Wistar , Proteínas Inativadoras de Ribossomos Tipo 1 , SaporinasRESUMO
Because of the low percentage of crashes involving buses and the assumption that public transport improves road safety by reducing vehicular traffic, public interest in bus safety is not as great as that in the safety of other types of vehicles. It is possible that less attention is paid to the significance of crashes involving buses because the safety level of bus systems is considered to be adequate. The purpose of this study was to evaluate the knowledge and perceptions of bus managers with respect to safety issues and the potential effectiveness of various technologies in achieving higher safety standards. Bus managers were asked to give their opinions on safety issues related to drivers (training, skills, performance evaluation and behaviour), vehicles (maintenance and advanced devices) and roads (road and traffic safety issues) in response to a research survey. Kendall's algorithm was used to evaluate the level of concordance. The results showed that the majority of the proposed items were considered to have great potential for improving bus safety. The data indicated that in the experience of the participants, passenger unloading and pedestrians crossing near bus stops are the most dangerous actions with respect to vulnerable users. The final results of the investigation showed that start inhibition, automatic door opening, and the materials and internal architecture of buses were considered the items most strongly related to bus passenger safety. Brake assistance and vehicle monitoring systems were also considered to be very effective. With the exception of driver assistance systems for passenger and pedestrian safety, the perceptions of the importance of other driver assistance systems for vehicle monitoring and bus safety were not unanimous among the bus company managers who participated in this survey. The study results showed that the introduction of new technologies is perceived as an important factor in improving bus safety, but a better understanding of their actual effectiveness and related risk factor avoidance must be developed to permit their useful implementation in bus fleets.
Assuntos
Acidentes de Trânsito/prevenção & controle , Atitude Frente a Saúde , Condução de Veículo/normas , Planejamento Ambiental/normas , Veículos Automotores/normas , Segurança/normas , Prevenção de Acidentes/instrumentação , Prevenção de Acidentes/métodos , Acidentes de Trânsito/psicologia , Algoritmos , Condução de Veículo/psicologia , Técnica Delphi , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Itália , Inquéritos e QuestionáriosRESUMO
Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain.
Assuntos
Córtex Cerebral/fisiopatologia , Exercício Físico , Condicionamento Físico Animal/fisiologia , Traumatismos da Medula Espinal/terapia , Adenilil Ciclases/metabolismo , Adenilil Ciclases/fisiologia , Animais , Animais Recém-Nascidos , Mapeamento Encefálico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Membro Posterior/metabolismo , Membro Posterior/fisiologia , Humanos , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/fisiopatologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
BACKGROUND: Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification. METHODS: We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions. RESULTS: Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs. CONCLUSIONS: miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS.
Assuntos
Síndromes da Dor Regional Complexa/genética , MicroRNAs/genética , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Síndromes da Dor Regional Complexa/sangue , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/sangue , Inflamação/genética , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Estatística como AssuntoRESUMO
In Europe, approximately 60% of road accident fatalities occur on two-lane rural roads. Thus, research to develop and enhance explanatory and predictive models for this road type continues to be of interest in mitigating these accidents. To this end, this paper describes a novel and extensive data collection and modeling effort to define accident models for two-lane road sections based on a unique combination of exposure, geometry, consistency and context variables directly related to the safety performance. The first part of the paper documents how these were identified for the segmentation of highways into homogeneous sections. Next, is a description of the extensive data collection effort that utilized differential cinematic GPS surveys to define the horizontal alignment variables, and road safety inspections (RSIs) to quantify the other road characteristics related to safety. The final part of the paper focuses on the calibration of models for estimating the expected number of accidents on homogeneous sections that can be characterized by constant values of the explanatory variables. Several candidate models were considered for calibration using the Generalized Linear Modeling (GLM) approach. After considering the statistical significance of the parameters related to exposure, geometry, consistency and context factors, and goodness of fit statistics, 19 models were ranked and three were selected as the recommended models. The first of the three is a base model, with length and traffic as the only predictor variables; since these variables are the only ones likely to be available network-wide, this base model can be used in an empirical Bayesian calculation to conduct network screening for ranking "sites with promise" of safety improvement. The other two models represent the best statistical fits with different combinations of significant variables related to exposure, geometry, consistency and context factors. These multiple variable models can be used, with caution, and in conjunction with results from other studies, to derive accident modification factors for these variables for design applications, and in safety assessment for smaller samples of sites for which these variables can be assembled with relative ease.
Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/estatística & dados numéricos , Planejamento Ambiental/estatística & dados numéricos , População Rural , Teorema de Bayes , Calibragem , Humanos , Modelos Lineares , Análise Multivariada , Reprodutibilidade dos Testes , Medição de RiscoRESUMO
The mechanisms responsible for long-term, massive reorganization of representational maps in primate somatosensory cortex after deafferentation are poorly understood. Sprouting of cortical axons cannot account for the extent of reorganization, and withdrawal of axons of deafferented brainstem and thalamic neurons, permitting expression of previously silent synapses, has not been directly demonstrated. This study is focused on the second of these. In monkeys, deafferented for two years by section of the cuneate fasciculus at the C1 level, there was extensive withdrawal of axon terminals from thalamus and cortex, detectable a decade before visible atrophy of their parent neuronal somata in the cuneate nucleus or thalamus. Slow, inexorable progression of lemniscal and thalamocortical axonal withdrawal is a neurodegenerative phenomenon likely to be a powerful inducement to compensatory long-term plasticity, a mechanism that can explain the long-term evolution of cortical reorganization and, with it, phantom sensations in spinal patients and amputees.
Assuntos
Axônios/patologia , Córtex Cerebral/patologia , Traumatismos dos Nervos Periféricos , Vias Aferentes/patologia , Vias Aferentes/fisiopatologia , Animais , Atrofia , Tronco Encefálico/patologia , Tronco Encefálico/fisiopatologia , Córtex Cerebral/fisiopatologia , Denervação , Macaca mulatta , Bulbo/patologia , Bulbo/fisiopatologia , Plasticidade Neuronal , Neurônios/patologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Terminações Pré-Sinápticas/patologia , Córtex Somatossensorial/patologia , Córtex Somatossensorial/fisiopatologia , Tálamo/patologia , Tálamo/fisiopatologia , Fatores de TempoRESUMO
The ventral posterior nucleus of the thalamus (VP) receives two major sets of excitatory inputs, one from the ascending somatosensory pathways originating in the dorsal horn, dorsal column nuclei, and trigeminal nuclei, and the other originating from the cerebral cortex. Both systems use glutamate as neurotransmitter, as do the thalamocortical axons relaying somatosensory information from the VP to the primary somatosensory cortex (SI). The synapses formed by these projection systems differ anatomically, physiologically, and in their capacity for short-term synaptic plasticity. Glutamate uptake into synaptic vesicles and its release at central synapses depend on two isoforms of vesicular glutamate transporters, VGluT1 and VGluT2. Despite ample evidence of their complementary distribution, some instances exist of co-localization in the same brain areas or at the same synapses. In the thalamus, the two transcripts coexist in cells of the VP and other nuclei but not in the posterior or intralaminar nuclei. We show that the two isoforms are completely segregated at VP synapses, despite their widespread expression throughout the dorsal and ventral thalamus. We present immunocytochemical, ultrastructural, gene expression, and connectional evidence that VGluT1 in the VP is only found at corticothalamic synapses, whereas VGluT2 is only found at terminals made by axons originating in the spinal cord and brainstem. By contrast, the two VGluT isoforms are co-localized in thalamocortical axon terminals targeting layer IV, but not in those targeting layer I, suggesting the presence of two distinct projection systems related to the core/matrix pattern of organization of thalamocortical connectivity described in other mammals.
Assuntos
Ácido Glutâmico/metabolismo , Terminações Pré-Sinápticas/metabolismo , Núcleos Ventrais do Tálamo/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Vias Aferentes/metabolismo , Vias Aferentes/ultraestrutura , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Mapeamento Encefálico/métodos , Tronco Encefálico/metabolismo , Tronco Encefálico/ultraestrutura , Vias Eferentes/metabolismo , Vias Eferentes/ultraestrutura , Expressão Gênica/fisiologia , Hibridização In Situ , Camundongos , Microscopia Confocal , Microscopia Imunoeletrônica , Terminações Pré-Sinápticas/ultraestrutura , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Córtex Somatossensorial/metabolismo , Córtex Somatossensorial/ultraestrutura , Medula Espinal/metabolismo , Medula Espinal/ultraestrutura , Transmissão Sináptica/fisiologia , Núcleos Ventrais do Tálamo/ultraestrutura , Proteína Vesicular 1 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/genéticaRESUMO
To acquire knowledge about the environment two types of learning are necessary: declarative localizatory learning about where environmental cues and the subject are, and procedural learning about how to explore and move around the environment. Experimental data indicate that hippocampal regions are involved in spatial learning, playing a key role in building spatial cognitive maps. The contribution of hippocampal NMDA receptors to spatial functions is indicated by the disruption of place learning when NMDA long-term potentiation is blocked. Conversely, the hippocampal contribution to the acquisition of procedural strategies is still controversial. Inactivation of the hippocampus by antagonizing the activity of AMPA/kainate receptors results in impaired spatial procedural learning. However, in the presence of a blockade of NMDA long-term potentiation in hippocampal areas it is still possible to learn explorative strategies. To investigate the involvement of the hippocampal NMDA receptors in spatial procedural learning, an NMDA receptor antagonist (CGS 19755) was administered i.p. to unlesioned animals or to animals with total ablation of hippocampal structures that had been tested in the Morris water maze. The CGS administration induced peripheral circling in both unlesioned control animals and in rats with bilateral hippocampal ablation. Conversely, circling was not observed if the drug-treated animals (either unlesioned or lesioned) had been spatially trained before drug administration. These findings indicate that even in the absence of the hippocampal formation the NMDA receptor antagonist found a site of action to influence the acquisition of spatial procedures to search for the platform.
Assuntos
Lesões Encefálicas/patologia , Hipocampo/fisiopatologia , Aprendizagem/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Comportamento Espacial/fisiologia , Análise de Variância , Animais , Comportamento Animal , Antagonistas de Aminoácidos Excitatórios/farmacologia , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Ácidos Pipecólicos/farmacologia , Ratos , Ratos Wistar , Comportamento Espacial/efeitos dos fármacosRESUMO
The relay of pain fibers from the spinal and medullary dorsal horn in the thalamus has become a controversial issue. This study analyzed the relationship of fibers arising in lamina I to nuclei in and around the caudal pole of the ventral posterior nuclear complex and especially to a zone of calbindin-dense immunoreactivity (VMpo) identified by some authors as the sole thalamic relay for these fibers. We show that the densest zone of calbindin immunoreactivity is part of a more extensive, calbindin-immunoreactive region that lies well within the medial tip of the ventral posterior medial nucleus (VPM), as delineated by other staining methods, and prove that the use of different anti-calbindin antibodies cannot account for differences in interpretations of the organization of the posterior thalamic region. By combining immunocytochemical staining with anterograde tracing from injections involving lamina I, we demonstrate widespread fiber terminations that are not restricted to the calbindin-rich medial tip of VPM and show that the lamina I arising fibers are not themselves calbindin immunoreactive. This study disproves the existence of VMpo as an independent thalamic pain nucleus or as a specific relay in the ascending pain system.
Assuntos
Fibras Nervosas/química , Células do Corno Posterior/citologia , Proteína G de Ligação ao Cálcio S100/análise , Tratos Espinotalâmicos/química , Núcleos Ventrais do Tálamo/química , Núcleos Ventrais do Tálamo/citologia , Vias Aferentes , Animais , Especificidade de Anticorpos , Calbindinas , Proteínas de Ligação ao Cálcio/análise , Imuno-Histoquímica , Macaca mulatta , Núcleos Posteriores do Tálamo/química , Núcleos Posteriores do Tálamo/citologia , Proteína G de Ligação ao Cálcio S100/imunologia , Tratos Espinotalâmicos/citologia , Núcleos Talâmicos/química , Núcleos Talâmicos/citologiaRESUMO
A new paradigm of learning was developed through observational training in which rats repeatedly observed companion rats performing different spatial tasks. Observer animals were separately housed in small cages suspended over a water maze tank. They repeatedly observed companion actor rats performing spatial tasks differing according to the experimental requirements. After the observational training, observer animals were or not surgically hemicerebellectomized. This surgical ablation was performed to block any further acquisition of new behavioral strategies during actual performance of swimming task. When cerebellar symptomatology stabilized, observer animals were actually tested in the Morris Water Maze (MWM) task they had previously only observed. The observer rats displayed exploration abilities that closely matched the previously observed behaviors. The results obtained indicate that it is possible to learn complex behavioral strategies by observation using this new protocol. Furthermore, acquisition of the single facets that form the behavioral repertoire can be separately studied.
Assuntos
Comportamento Animal/fisiologia , Comportamento Imitativo/fisiologia , Aprendizagem em Labirinto/fisiologia , Testes Neuropsicológicos , Percepção Espacial/fisiologia , Animais , Cerebelo/lesões , Cerebelo/fisiologia , Cerebelo/cirurgia , Denervação , Procedimentos Neurocirúrgicos/instrumentação , Procedimentos Neurocirúrgicos/métodos , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
Notwithstanding the development of reliable tracking systems, the quantification methodology of the Morris water maze (MWM) has witnessed an operational mismatch between the indexes used to quantify MWM performance and the cognitive concepts derived from these indexes. Indeed, escape latency is the main, and often unique, performance measure used for the quantification of behavior. Aim of the present work was to overcome this limitation by presenting a methodology that allows for automatic categorical pattern recognition of the behavioral strategies performed in the MWM. By selecting few a priori and user-defined behavioral categories, many quantitative variables and regions of interest (ROIs), we used discriminant analysis (DA) to obtain 97.9% of correct automatic recognition of categories. The developed discriminant model (DM) also allowed to predict category membership of newly recorded swim paths with the same statistical efficacy (96%), and to identify the variables that better discriminate between adjacent categories. The combination of DA with a tracking system, a selection of many variables, different ROIs and qualitative categorization, reduces the gap between the measurement process and the categories used to describe a given behavior, and offers a methodology to computationally reproduce the human categorization of behaviors in the MWM.
Assuntos
Comportamento Exploratório/fisiologia , Aprendizagem em Labirinto/fisiologia , Reconhecimento Automatizado de Padrão , Animais , Cognição/fisiologia , Coleta de Dados , Masculino , Orientação/fisiologia , Ratos , Ratos Wistar , NataçãoRESUMO
Recent data demonstrate that the cerebellum contributes to the internal representation of action. This representation is used not only to generate motor actions, but also to understand and learn the actions and skills of others by imitation. The cerebellar networks appear to be indispensable for acquiring complex behaviors and procedures. The cerebellar role in the acquisition of procedural competencies is particularly evident in spatial information processing. The cerebellum allows acquiring by observation competencies in exploration behaviors as efficient as the competencies acquired by actually performing the same task. The specificity of the cerebellar role in the acquisition phases of learning by observation is demonstrated by the complete absence of spatial learning when the observational training is performed in presence of a cerebellar lesion. This datum is further corroborated by the evidence that, once acquired, spatial procedures can be efficiently performed even in the presence of cerebellar damage, in agreement with the neuroimaging findings of low cerebellar activation after prolonged practice. The finding that the cerebellum is involved in procedural acquisition and in observational learning allowed us to dissect a complex behavior into single behavioral units forming a complete procedural sequence, demonstrating that such behavioral units do exist and can be independently acquired.