Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus

<p>Abstract</p> <p>Background</p> <p>Status epilepticus (SE) is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus.</p> <p>Methods</p> <p>SE was induced by an intraperitoneal (i.p.) injection of kainic acid (KA) in 9- and 21-day-old (P9 and P21) rats. The mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9), glial-derived neurotrophic factor (GDNF), interferon gamma (IFN-γ), and transforming growth factor-beta 1 (TGF-β1) were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR). IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE.</p> <p>Results</p> <p>SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala.</p> <p>Conclusion</p> <p>Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the postnatal rat hippocampus. In the juvenile hippocampus, transient increases in cytokine mRNA expression after SE, in contrast to prolonged glial reactivity and region-specific microglial activity after SE, suggest that the inflammatory response is changed from a fulminant and general initial phase to a more moderate and specific subacute response.</p

Rapid Communication: Restriction Fragment Length Polymorphisms at the Porcine Transporter Associated with Antigen Processing 1 (TAP1) Locus

Source and Description of Probe. A 2.7-kb human cDNA clone for TAP1 was excised from the XbaI site of the plasmid pRSV.5neo (Spies et al., 1990). Method of Detection. Hybridizations were performed at 65°C for 16 to 20 h (10% dextran sulfate, 7% SDS, .263 M NazHP04, 1% BSA, 1 mM EDTA, 100 pg/mL sonicated denatured salmon sperm DNA). Final washes were done at 65°C in .7x SSC, .5% SDS for 15 to 20 min

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

Can ultrasound be used to stimulate nerve tissue?

BACKGROUND: The stimulation of nerve or cortical tissue by magnetic induction is a relatively new tool for the non-invasive study of the brain and nervous system. Transcranial magnetic stimulation (TMS), for example, has been used for the functional mapping of the motor cortex and may have potential for treating a variety of brain disorders. METHODS AND RESULTS: A new method of stimulating active tissue is proposed by propagating ultrasound in the presence of a magnetic field. Since tissue is conductive, particle motion created by an ultrasonic wave will induce an electric current density generated by Lorentz forces. An analytical derivation is given for the electric field distribution induced by a collimated ultrasonic beam. An example shows that peak electric fields of up to 8 V/m appear to be achievable at the upper range of diagnostic intensities. This field strength is about an order of magnitude lower than fields typically associated with TMS; however, the electric field gradients induced by ultrasound can be quite high (about 60 kV/m(2 )at 4 MHz), which theoretically play a more important role in activation than the field magnitude. The latter value is comparable to TMS-induced gradients. CONCLUSION: The proposed method could be used to locally stimulate active tissue by inducing an electric field in regions where the ultrasound is focused. Potential advantages of this method compared to TMS is that stimulation of cortical tissue could be highly localized as well as achieved at greater depths in the brain than is currently possible with TMS

A First Look at Rotation in Inactive Late-Type M Dwarfs

We have examined the relationship between rotation and activity in 14 late-type (M6-M7) M dwarfs, using high resolution spectra taken at the W.M. Keck Observatory and flux-calibrated spectra from the Sloan Digital Sky Survey. Most were selected to be inactive at a spectral type where strong H-alpha emission is quite common. We used the cross-correlation technique to quantify the rotational broadening; six of the stars in our sample have vsini > 3.5 km/s. Our most significant and perplexing result is that three of these stars do not exhibit H-alpha emission, despite rotating at velocities where previous work has observed strong levels of magnetic field and stellar activity. Our results suggest that rotation and activity in late-type M dwarfs may not always be linked, and open several additional possibilities including a rotationally-dependent activity threshold, or a possible dependence on stellar parameters of the Rossby number at which magnetic/activity "saturation" takes place in fully convective stars.Comment: 8 pages, 4 figures, accepted for publication in Ap

Subtle increases in heart size persist into adulthood in growth restricted babies: the Cardiovascular Risk in Young Finns Study

BACKGROUND AND OBJECTIVES: Impaired fetal growth is associated with increased cardiovascular morbidity and mortality in adulthood. We sought to determine whether adults born with intrauterine growth restriction have primary maladaptive changes in cardiac structure. METHODS: Study participants were adults (34-49 years) who attended the 31-year follow-up of the Cardiovascular Risk in Young Finns Study (longitudinal cohort). Transthoracic echocardiograms and demographic and cardiovascular risk surveys were completed for 157 adults born small for gestational age (SGA, birth weight <10th population centile) and 627 born average for gestational age (average for gestational age (AGA), birth weight 50th-90th population centile). RESULTS: Those born growth restricted had subtly enlarged hearts with indexed left ventricular (LV) end-systolic and end-diastolic diameters slightly greater in the SGA individuals than the AGA group (LVESD 18.7 mm/m(2) SGA vs 18.1 mm/m(2) AGA, p<0.01; LVEDD 27.5 mm/m(2) SGA vs 26.6 mm/m(2) AGA, p<0.01); LV base-to-apex length (47.4 mm/m(2) SGA vs 46.0 mm/m(2) AGA, p<0.01); LV basal diameter (26.4 mm/m(2) SGA vs 25.7 mm/m(2) AGA, p<0.01); and right ventricular base-to-apex length (40.1 mm/m(2) SGA vs 39.2 mm/m(2) AGA, p=0.02). LV stroke volume was greater in those born AGA (74.5 mL SGA vs 78.8 mL AGA, p<0.01), with no significant difference in cardiac output (5 L/min SGA vs 5.2 L/min AGA, p=0.06), heart rate, diastolic indices or sphericity index. CONCLUSIONS: Adults born SGA have some statistically significant but subtle changes in cardiac structure and function, which are less marked than have been described in childhood, and are unlikely to play a pathogenic role in their elevated cardiovascular risk

Effect of functional feeds on fatty acid and eicosanoid metabolism in liver and head kidney of Atlantic salmon (Salmo salar L.) with experimentally induced Heart and Skeletal Muscle Inflammation

Heart and Skeletal Muscle Inflammation (HSMI) is an emerging viral disease caused by a novel Atlantic salmon reovirus (ASRV) affecting farmed fish. Primary symptoms associated with HSMI include myocardial and skeletal muscle necrosis indicating a severe inflammatory process. Recently, we applied the concept of clinical nutrition to moderate the long-term inflammatory process associated with HSMI in salmon subjected to experimental ASRV challenge. The use of functional feeds with lower lipid (hence energy) content reduced the inflammatory response to ASRV infection and the severity of associated heart lesions. The aim of the present study was to elucidate possible mechanisms underpinning the observed effects of the functional feeds, focussing on eicosanoid and fatty acid metabolism in liver and head kidney. Here we show that liver was also a site for histopathological lesions in HSMI showing steatosis reflecting impaired lipid metabolism. This study is also the first to evaluate the expression of a suite of key genes involved in pathways relating diet and membrane phospholipid fatty acid compositions, and the inflammatory response after ASRV infection. The expression of hepatic &Delta;6 and &Delta;5 desaturases was higher in fish fed the functional feeds, potentially increasing their capacity for endogenous production and availability of anti-inflammatory EPA. Effects on mobilization of lipids and changes in the LC-PUFA composition of membrane phospholipids, along with significant changes in the expression of the genes related to eicosanoid pathways, showed the important role of the head kidney in inflammatory diseases caused by viral infections. The results from the present study suggest that clinical nutrition through functional feeding could be an effective complementary therapy for emerging salmon viral diseases associated with long-term inflammation

Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure

Background-Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. Methods and Results-We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. Conclusions-Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure.Peer reviewe

Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs

The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI

Team sports performance analysed through the lens of social network theory: implications for research and practice

This paper discusses how social network analyses and graph theory can be implemented in team sports performance analyses to evaluate individual (micro) and collective (macro) performance data, and how to use this information for designing practice tasks. Moreover, we briefly outline possible limitations of social network studies and provide suggestions for future research. Instead of cataloguing discrete events or player actions, it has been argued that researchers need to consider the synergistic interpersonal processes emerging between teammates in competitive performance environments. Theoretical assumptions on team coordination prompted the emergence of innovative, theoretically-driven methods for assessing collective team sport behaviours. Here, we contribute to this theoretical and practical debate by conceptualising sports teams as complex social networks. From this perspective, players are viewed as network nodes, connected through relevant information variables (e.g., a ball passing action), sustaining complex patterns of interaction between teammates (e.g., a ball passing network). Specialized tools and metrics related to graph theory could be applied to evaluate structural and topological properties of interpersonal interactions of teammates, complementing more traditional analysis methods. This innovative methodology moves beyond use of common notation analysis methods, providing a richer understanding of the complexity of interpersonal interactions sustaining collective team sports performance. The proposed approach provides practical applications for coaches, performance analysts, practitioners and researchers by establishing social network analyses as a useful approach for capturing the emergent properties of interactions between players in sports teams