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Understanding how atoms interact with hot dense matter is essential for astrophysical and laboratory plasmas. Interactions in high-density plasmas broaden spectral lines, providing a rare window into interactions that govern, for example, radiation transport in stars. However, up to now, spectral line-shape theories employed at least one of three common approximations: second-order Taylor treatment of broadening operator, dipole-only interactions between atom and plasma, and classical treatment of perturbing electrons. In this Letter, we remove all three approximations simultaneously for the first time and test the importance for two applications: neutral hydrogen and highly ionized magnesium and oxygen. We found 15%-50% change in the spectral line widths, which are sufficient to impact applications including white-dwarf mass determination, stellar-opacity research, and laboratory plasma diagnostics.
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Nearly a century ago it was recognized that radiation absorption by stellar matter controls the internal temperature profiles within stars. Laboratory opacity measurements, however, have never been performed at stellar interior conditions, introducing uncertainties in stellar models. A particular problem arose when refined photosphere spectral analysis led to reductions of 30-50 per cent in the inferred amounts of carbon, nitrogen and oxygen in the Sun. Standard solar models using the revised element abundances disagree with helioseismic observations that determine the internal solar structure using acoustic oscillations. This could be resolved if the true mean opacity for the solar interior matter were roughly 15 per cent higher than predicted, because increased opacity compensates for the decreased element abundances. Iron accounts for a quarter of the total opacity at the solar radiation/convection zone boundary. Here we report measurements of wavelength-resolved iron opacity at electron temperatures of 1.9-2.3 million kelvin and electron densities of (0.7-4.0) × 10(22) per cubic centimetre, conditions very similar to those in the solar region that affects the discrepancy the most: the radiation/convection zone boundary. The measured wavelength-dependent opacity is 30-400 per cent higher than predicted. This represents roughly half the change in the mean opacity needed to resolve the solar discrepancy, even though iron is only one of many elements that contribute to opacity.
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Accurate calculation of spectral line broadening is important for many hot, dense plasma applications. However, calculated line widths have significantly underestimated measured widths for Δn=0 lines of Li-like ions, which is known as the isolated-line problem. In this Letter, scrutinization of the line-width derivation reveals that the commonly used expression neglects a potentially important contribution from electron-capture. Line-width calculations including this process are performed with two independent codes, both of which removed the discrepancies at temperatures below 10 eV. The revised calculations also suggest the remaining discrepancy scales more strongly with electron temperature than the atomic number as was previously suggested.
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We report on the first accurate validation of low-Z ion-stopping formalisms in the regime ranging from low-velocity ion stopping-through the Bragg peak-to high-velocity ion stopping in well-characterized high-energy-density plasmas. These measurements were executed at electron temperatures and number densities in the range of 1.4-2.8 keV and 4×10^{23}-8×10^{23} cm^{-3}, respectively. For these conditions, it is experimentally demonstrated that the Brown-Preston-Singleton formalism provides a better description of the ion stopping than other formalisms around the Bragg peak, except for the ion stopping at v_{i}â¼0.3v_{th}, where the Brown-Preston-Singleton formalism significantly underpredicts the observation. It is postulated that the inclusion of nuclear-elastic scattering, and possibly coupled modes of the plasma ions, in the modeling of the ion-ion interaction may explain the discrepancy of â¼20% at this velocity, which would have an impact on our understanding of the alpha energy deposition and heating of the fuel ions, and thus reduce the ignition threshold in an ignition experiment.
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The first systematic study of opacity dependence on atomic number at stellar interior temperatures is used to evaluate discrepancies between measured and modeled iron opacity [J. E. Bailey et al., Nature (London) 517, 56 (2015)NATUAS0028-083610.1038/nature14048]. High-temperature (>180 eV) chromium and nickel opacities are measured with ±6%-10% uncertainty, using the same methods employed in the previous iron experiments. The 10%-20% experiment reproducibility demonstrates experiment reliability. The overall model-data disagreements are smaller than for iron. However, the systematic study reveals shortcomings in models for density effects, excited states, and open L-shell configurations. The 30%-45% underestimate in the modeled quasicontinuum opacity at short wavelengths was observed only from iron and only at temperature above 180 eV. Thus, either opacity theories are missing physics that has nonmonotonic dependence on the number of bound electrons or there is an experimental flaw unique to the iron measurement at temperatures above 180 eV.
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The interpretation of x-ray spectra emerging from x-ray binaries and active galactic nuclei accreted plasmas relies on complex physical models for radiation generation and transport in photoionized plasmas. These models have not been sufficiently experimentally validated. We have developed a highly reproducible benchmark experiment to study spectrum formation from a photoionized silicon plasma in a regime comparable to astrophysical plasmas. Ionization predictions are higher than inferred from measured absorption spectra. Self-emission measured at adjustable column densities tests radiation transport effects, demonstrating that the resonant Auger destruction assumption used to interpret black hole accretion spectra is inaccurate.
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Accurate understanding of x-ray diagnostics is crucial for both interpreting high-energy-density experiments and testing simulations through quantitative comparisons. X-ray diagnostic models are complex. Past treatments of individual x-ray diagnostics on a case-by-case basis have hindered universal diagnostic understanding. Here, we derive a general formula for modeling the absolute response of non-focusing x-ray diagnostics, such as x-ray imagers, one-dimensional space-resolved spectrometers, and x-ray power diagnostics. The present model is useful for both data modeling and data processing. It naturally accounts for the x-ray crystal broadening. The new model verifies that standard approaches for a crystal response can be good approximations, but they can underestimate the total reflectivity and overestimate spectral resolving power by more than a factor of 2 in some cases near reflectivity edge features. We also find that a frequently used, simplified-crystal-response approximation for processing spectral data can introduce an absolute error of more than an order of magnitude and the relative spectral radiance error of a factor of 3. The present model is derived with straightforward geometric arguments. It is more general and is recommended for developing a unified picture and providing consistent treatment over multiple x-ray diagnostics. Such consistency is crucial for reliable multi-objective data analyses.
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Laboratory experiments typically test opacity models by measuring spectrally resolved transmission of a sample using bright backlight radiation. A potential problem is that any unaccounted background signal contaminating the spectrum will artificially reduce the inferred opacity. Methods developed to measure background signals in opacity experiments at the Sandia Z facility are discussed. Preliminary measurements indicate that backgrounds are 9%-11% of the backlight signal at wavelengths less than 10 Å. Background is thus a relatively modest correction for all Z opacity data published to date. Future work will determine how important background is at longer wavelengths.
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BACKGROUND: Obesity and diabetes are well-established risk factors of Alzheimer's disease (AD). In the brains of patients with AD and model mice, diabetes-related factors have been implicated in the pathological changes of AD. However, the molecular mechanistic link between the peripheral metabolic state and AD pathophysiology have remained elusive. Endoplasmic reticulum (ER) stress is known as one of the major contributors to the metabolic abnormalities in obesity and diabetes. Interventions aimed at reducing ER stress have been shown to improve the systemic metabolic abnormalities, although their effects on the AD pathology have not been extensively studied. OBJECTIVES: We examined whether interventions targeting ER stress attenuate the obesity/diabetes-induced Aß accumulation in brains. We also aimed to determine whether ER stress that took place in the peripheral tissues or central nervous system was more important in the Aß neuropathology. Furthermore, we explored if age-related metabolic abnormalities and Aß accumulation could be suppressed by reducing ER stress. METHODS: APP transgenic mice (A7-Tg), which exhibit Aß accumulation in the brain, were used as a model of AD to analyze parameters of peripheral metabolic state, ER stress, and Aß pathology in the brain. Intraperitoneal or intracerebroventricular administration of taurodeoxycholic acid (TUDCA), a chemical chaperone, was performed in high-fat diet (HFD)-fed A7-Tg mice for ~1 month, followed by analyses at 9 months of age. Mice fed a normal diet were treated with TUDCA by drinking water for 4 months and intraperitoneally for 1 month in parallel, and analyzed at 15 months of age. RESULTS: Intraperitoneal administration of TUDCA suppressed ER stress in the peripheral tissues and ameliorated the HFD-induced obesity and insulin resistance. Concomitantly, Aß levels in the brain were significantly reduced. In contrast, intracerebroventricular administration of TUDCA had no effect on the Aß levels. Peripheral administration of TUDCA was also effective against the age-related obesity and insulin resistance, and markedly reduced amyloid accumulation. CONCLUSIONS: Interventions that target peripheral ER stress might be beneficial therapeutic and prevention strategies against brain Aß pathology associated with metabolic overload and aging.
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Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Antivirais/administração & dosagem , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácido Tauroquenodesoxicólico/administração & dosagem , Doença de Alzheimer/prevenção & controle , Animais , Antivirais/farmacologia , Encéfalo/metabolismo , Dieta , Modelos Animais de Doenças , Humanos , Infusões Intraventriculares , Injeções Intraperitoneais , Camundongos , Camundongos Transgênicos , Ácido Tauroquenodesoxicólico/farmacologiaRESUMO
We report experimental and modeling results for the charge state distribution of laboratory photoionized neon plasmas in the first systematic study over nearly an order of magnitude range of ionization parameter ξâF/N_{e}. The range of ξ is achieved by flexibility in the experimental platform to adjust either the x-ray drive flux F at the sample or the electron number density N_{e} or both. Experimental measurements of photoionized plasma conditions over such a range of parameters enable a stringent test of atomic kinetics models used within codes that are applied to photoionized plasmas in the laboratory and astrophysics. From experimental transmission data, ion areal densities are extracted by spectroscopic analysis that is independent of atomic kinetics modeling. The measurements reveal the net result of the competition between photon-driven ionization and electron-driven recombination atomic processes as a function of ξ as it affects the charge state distribution. Results from radiation-hydrodynamics modeling calculations with detailed inline atomic kinetics modeling are compared with the experimental results. There is good agreement in the mean charge and overall qualitative similarities in the trends observed with ξ but significant quantitative differences in the fractional populations of individual ions.
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Iron opacity calculations presently disagree with measurements at an electron temperature of â¼180-195 eV and an electron density of (2-4)×10^{22}cm^{-3}, conditions similar to those at the base of the solar convection zone. The measurements use x rays to volumetrically heat a thin iron sample that is tamped with low-Z materials. The opacity is inferred from spectrally resolved x-ray transmission measurements. Plasma self-emission, tamper attenuation, and temporal and spatial gradients can all potentially cause systematic errors in the measured opacity spectra. In this article we quantitatively evaluate these potential errors with numerical investigations. The analysis exploits computer simulations that were previously found to reproduce the experimentally measured plasma conditions. The simulations, combined with a spectral synthesis model, enable evaluations of individual and combined potential errors in order to estimate their potential effects on the opacity measurement. The results show that the errors considered here do not account for the previously observed model-data discrepancies.
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We set out to ascertain whether uterine carcinosarcoma represents: (a) a "collision tumor," i.e., a mixture of two histogenetically distinct malignant cell populations (endometrial carcinoma and sarcoma); (b) a "combination tumor" with both histological elements of common stem cell origin; or (c) a "composition tumor," i.e., an endometrial carcinoma with reactive, atypical stroma. In in vitro cultures of human uterine carcinosarcoma, we could separate two distinct, different cell types and succeeded in establishing adenocarcinoma cell lines (HWUA-1 and HWUA-2) and sarcoma cell lines (HWUS-1, HWUS-1a, and HWUS-2). These cell lines grew well for over 10 months. HWUS-1a was hypertetraploid, HWUA-1 and HWUA-2 were pseudodiploid, and HWUS-1 and HWUS-2 were hyperdiploid. These cell lines were transplanted into the subcutis of BALB/c nude mice and produced tumors. HWUA-1 and HWUA-2 cell produced poorly differentiated adenocarcinoma, HWUS-1 and HWUS-2 produced poorly differentiated sarcoma, and HWUS-1a produced well-differentiated leiomyosarcoma. These results support the combination tumor theory and reject the composition tumor theory as the cause of carcinosarcoma.
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Carcinossarcoma/patologia , Neoplasias Uterinas/patologia , Adenocarcinoma/patologia , Animais , Divisão Celular , Linhagem Celular , Células Cultivadas , Feminino , Humanos , Cariotipagem , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Sarcoma/patologia , Transplante HeterólogoRESUMO
Recently, frequency-resolved iron opacity measurements at electron temperatures of 170-200 eV and electron densities of (0.7-4.0)×10(22)cm(-3) revealed a 30-400% disagreement with the calculated opacities [J. E. Bailey et al., Nature (London) 517, 56 (2015)]. The discrepancies have a high impact on astrophysics, atomic physics, and high-energy density physics, and it is important to verify our understanding of the experimental platform with simulations. Reliable simulations are challenging because the temporal and spatial evolution of the source radiation and of the sample plasma are both complex and incompletely diagnosed. In this article, we describe simulations that reproduce the measured temperature and density in recent iron opacity experiments performed at the Sandia National Laboratories Z facility. The time-dependent spectral irradiance at the sample is estimated using the measured time- and space-dependent source radiation distribution, in situ source-to-sample distance measurements, and a three-dimensional (3D) view-factor code. The inferred spectral irradiance is used to drive 1D sample radiation hydrodynamics simulations. The images recorded by slit-imaged space-resolved spectrometers are modeled by solving radiation transport of the source radiation through the sample. We find that the same drive radiation time history successfully reproduces the measured plasma conditions for eight different opacity experiments. These results provide a quantitative physical explanation for the observed dependence of both temperature and density on the sample configuration. Simulated spectral images for the experiments without the FeMg sample show quantitative agreement with the measured spectral images. The agreement in spectral profile, spatial profile, and brightness provides further confidence in our understanding of the backlight-radiation time history and image formation. These simulations bridge the static-uniform picture of the data interpretation and the dynamic-gradient reality of the experiments, and they will allow us to quantitatively assess the impact of effects neglected in the data interpretation.
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We report experimental results and simulations showing efficient laser energy coupling into plasmas at conditions relevant to the magnetized liner inertial fusion (MagLIF) concept. In MagLIF, to limit convergence and increase the hydrodynamic stability of the implosion, the fuel must be efficiently preheated. To determine the efficiency and physics of preheating by a laser, an Ar plasma with n_{e}/n_{crit}â¼0.04 is irradiated by a multi-ns, multi-kJ, 0.35-µm, phase-plate-smoothed laser at spot-averaged intensities ranging from 1.0×10^{14} to 2.5×10^{14}W/cm^{2} and pulse widths from 2 to 10 ns. Time-resolved x-ray images of the laser-heated plasma are compared to two-dimensional radiation-hydrodynamic simulations that show agreement with the propagating emission front, a comparison that constrains laser energy deposition to the plasma. The experiments show that long-pulse, modest-intensity (I=1.5×10^{14}W/cm^{2}) beams can efficiently couple energy (â¼82% of the incident energy) to MagLIF-relevant long-length (9.5 mm) underdense plasmas. The demonstrated heating efficiency is significantly higher than is thought to have been achieved in early integrated MagLIF experiments [A. B. Sefkow et al., Phys. Plasmas 21, 072711 (2014)10.1063/1.4890298].
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Nuclear changes, including internucleosomal DNA fragmentation, are characteristic features of neuronal apoptosis resulting from transient cerebral ischemia and related brain insults for which the molecular mechanism has not been elucidated. Recent studies suggest that a caspase-3-mediated mechanism may be involved in the process of nuclear degradation in ischemic neurons. In this study, we cloned from rat brain a homolog cDNA encoding caspase-activated deoxyribonuclease (CAD)/DNA fragmentation factor 40 (DFF40), a 40 kDa nuclear enzyme that is activated by caspase-3 and promotes apoptotic DNA degradation. Subsequently, we investigated the role of CAD/DFF40 in the induction of internucleosomal DNA fragmentation in the hippocampus in a rat model of transient global ischemia and in primary neuronal cultures under ischemia-like conditions. At 8-72 hr after ischemia, CAD/DFF40 mRNA and protein were induced in the degenerating hippocampal CA1 neurons. CAD/DFF40 formed a heterodimeric complex in the nucleus with its natural inhibitor CAD (ICAD) and was activated after ischemia in a delayed manner (>24 hr) by caspase-3, which translocated into the nucleus and cleaved ICAD. Furthermore, an induced CAD/DFF40 activity was detected in nuclear extracts in both in vivo and in vitro models, and the DNA degradation activity of CAD/DFF40 was inhibited by purified ICAD protein. These results strongly suggest that CAD/DFF40 is the endogenous endonuclease that mediates caspase-3-dependent internucleosomal DNA degradation and related nuclear alterations in ischemic neurons.
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Apoptose , Caspases/metabolismo , Fragmentação do DNA/fisiologia , Desoxirribonucleases/metabolismo , Ataque Isquêmico Transitório/metabolismo , Neurônios/metabolismo , Animais , Proteínas Reguladoras de Apoptose , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Caspase 3 , Células Cultivadas , Clonagem Molecular , Fragmentação do DNA/efeitos dos fármacos , Desoxirribonucleases/genética , Regulação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Dados de Sequência Molecular , Neurônios/citologia , Neurônios/efeitos dos fármacos , Especificidade de Órgãos , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas/metabolismo , Proteínas/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de AminoácidosRESUMO
Temperature and density asymmetry diagnosis is critical to advance inertial confinement fusion (ICF) science. A multi-monochromatic x-ray imager (MMI) is an attractive diagnostic for this purpose. The MMI records the spectral signature from an ICF implosion core with time resolution, 2-D space resolution, and spectral resolution. While narrow-band images and 2-D space-resolved spectra from the MMI data constrain temperature and density spatial structure of the core, the accuracy of the images and spectra depends not only on the quality of the MMI data but also on the reliability of the post-processing tools. Here, we synthetically quantify the accuracy of images and spectra reconstructed from MMI data. Errors in the reconstructed images are less than a few percent when the space-resolution effect is applied to the modeled images. The errors in the reconstructed 2-D space-resolved spectra are also less than a few percent except those for the peripheral regions. Spectra reconstructed for the peripheral regions have slightly but systematically lower intensities by â¼6% due to the instrumental spatial-resolution effects. However, this does not alter the relative line ratios and widths and thus does not affect the temperature and density diagnostics. We also investigate the impact of the pinhole size variation on the extracted images and spectra. A 10% pinhole size variation could introduce spatial bias to the images and spectra of â¼10%. A correction algorithm is developed, and it successfully reduces the errors to a few percent. It is desirable to perform similar synthetic investigations to fully understand the reliability and limitations of each MMI application.
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The authors investigated the role of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in the mechanisms of focal cerebral ischemia and its interaction with inducible nitric oxide synthase (iNOS). Focal cerebral ischemia was produced by permanent occlusion of the middle cerebral artery (MCA) in mice. Infarct volume was measured 96 hours later by computer-assisted planimetry in thionin-stained brain sections. The highly selective COX-2 inhibitor NS398 (20 mg/kg; intraperitoneally), administered twice a day starting 6 hours after MCA occlusion, reduced total infarct volume in C57BL/6 (-23%) and 129/SVeV mice (-21%), and ameliorated the motor deficits produced by MCA occlusion (P < .05). However, NS398 did not influence infarct volume in mice with deletion of the iNOS gene (P > .05). In contrast, the neuronal NOS inhibitor 7-NI (50 mg/kg; intraperitoneally), administered once 5 minutes after MCA occlusion, reduced neocortical infarct volume by 20% in iNOS -/- mice (P < .05). NS398 did not affect arterial pressure, resting CBF or the CBF reactivity to hypercapnia in anesthetized iNOS null mice (P > .05). The data suggest that COX-2 reaction products, in mouse as in rat, contribute to ischemic brain injury. However, the failure of NS398 to reduce infarct volume in iNOS null mice suggests that iNOS-derived NO is required for the deleterious effects of COX-2 to occur. Thus, COX-2 reaction products may be another mechanism by which iNOS-derived NO contributes to ischemic brain injury.
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Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Inibidores de Ciclo-Oxigenase/farmacologia , Isoenzimas/metabolismo , Óxido Nítrico Sintase/genética , Nitrobenzenos/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Sulfonamidas/farmacologia , Animais , Isquemia Encefálica/metabolismo , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Deleção de Genes , Camundongos , Camundongos Knockout , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , RatosRESUMO
The authors investigated the influence of age on the outcome of cerebral ischemia in wild-type mice and in mice with a deletion of the inducible nitric oxide synthase (iNOS) gene. The middle cerebral artery was permanently occluded in iNOS-null mice and in wild-type (C57BL/6) controls aged 4, 8, 16, and 24 weeks. Infarct volume was determined in thionin-stained brain sections 4 days after permanent middle cerebral artery occlusion. No differences in forebrain volume were found among wild-type and iNOS-null mice at the ages studied (P > 0.05). In C57BL/6 mice (n = 5 to 6/group), neocortical infarct volume corrected for swelling was 28 +/- 5 mm3 in 4-week-old mice, 28 +/- 3 at 8 weeks, 35 +/- 4 at 16 weeks, and 37 +/- 6 at 24 weeks (mean +/- SD). iNOS-null mice (n = 5 to 6/group) had smaller infarcts than wild-type controls at all ages (P < 0.05). However, the magnitude of the reduction was greater in 4-week-old (-29% +/- 10%) or 8-week-old mice (-24% +/- 8%), than in 16-week-old (-14% +/- 10%) or 24-week-old mice (-11% +/- 6%). Neurologic deficit scores improved significantly between 24 and 96 hours in 4- and 8-week-old iNOS-null mice compared with age-matched wild-type mice (P < 0.05). However, in 16- or 24-week-old iNOS-null mice, neurologic deficits did not improve (P > 0.05). The authors conclude that in iNOS-/- and in wild-type mice, the size of the infarct produced by occlusion of the middle cerebral artery is larger in older than in younger mice. However, the reduction in infarct volume observed in iNOS-null mice is age-dependent and is greatest at 1 to 2 months of age. Therefore, age is a critical variable in studies of focal cerebral ischemic damage, both in wild-type mice and in mouse mutants.
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Envelhecimento/patologia , Isquemia Encefálica/patologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/fisiologia , Animais , Peso Corporal/fisiologia , Encéfalo/patologia , Artérias Cerebrais/fisiologia , Infarto Cerebral/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase/deficiência , Óxido Nítrico Sintase Tipo II , Prosencéfalo/enzimologia , Prosencéfalo/patologia , Fatores de TempoRESUMO
Cell death-regulatory genes like caspases and bcl-2 family genes are involved in delayed cell death in the CA1 sector of hippocampus after global cerebral ischemia, but little is known about the mechanisms that trigger their expression. The authors found that expression of Fas and Fas-ligand messenger ribonucleic acid and protein was induced in vulnerable CA1 neurons at 24 and 72 hours after global ischemia. Fas-associating protein with a novel death domain (FADD) also was upregulated and immunoprecipitated and co-localized with Fas. Caspase-10 was activated and interacted with FADD protein to an increasing extent as the duration of ischemia increased. Moreover, caspase-10 co-localized with both FADD and caspase-3. These findings suggest that Fas-mediated death signaling may play an important role in signaling hippocampal neuronal death in CA1 after global cerebral ischemia.