Aging and microglial response following systemic stimulation with escherichia coli in mice

Systemic infection is an important risk factor for the development cognitive impairment and neurodegeneration in older people. Animal experiments show that systemic challenges with live bacteria cause a neuro-inflammatory response, but the effect of age on this response in these models is unknown. Young (2 months) and middle-aged mice (13-14 months) were intraperitoneally challenged with live Escherichia coli (E. coli) or saline. The mice were sacrificed at 2, 3 and 7 days after inoculation; for all time points, the mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h after inoculation. Microglial response was monitored by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry, and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators. We observed an increased microglial cell number and moderate morphologically activated microglial cells in middle-aged mice, as compared to young mice, after intraperitoneal challenge with live E. coli. Flow cytometry of microglial cells showed higher CD45 and CD11b expressions in middle-aged infected mice compared to young infected mice. The brain expression levels of pro-inflammatory genes were higher in middle-aged than in young infected mice, while middle-aged infected mice had similar expression levels of these genes in the systemic compartment. We conclude that systemic challenge with live bacteria causes an age-dependent neuro-inflammatory and microglial response. Our data show signs of an age-dependent disconnection of the inflammatory transcriptional signature between the brain and the systemic compartment.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Histopathology of bacterial meningitis:Snapshots of the brain

Bacterial meningitis shows histopathological characteristics that are specific to each causative agent. Identifying these specific characteristics is important because it adds to the knowledge about the pathophysiology of tissue damage by the various causative agents. This could possibly lead to the development of new, more effective treatments. We studied 31 cases of pneumococcal meningitis and the specific histopathological characteristics were described, namely: inflammation of the medium and large arteries, intraparenchymal bleeding, cerebritis, thrombosis, and infarctions. Of these characteristics, inflammation of medium and large arteries is not only practically universally present, but is also clearly associated with thrombosis and infarctions. This suggests that vascular damage plays a key role in the pathophysiology of brain damage in pneumococcal meningitis. The study of 4 autopsy cases of pneumococcal meningitis with catastrophic cebrovascular complications after initially successful recovery showed that its etiology is multifactorial with vascular inflammation, thromboembolism in the large arteries and infectious intracranial aneurysms. The observation that Streptococcus pneumoniae could be detected intra- and extracellularly (individually or in groups) in patients treated with antibiotics (up to 35 days in length) is striking. We studied the histopathological characteristics of listeria meningitis with the same methodology and the observations show that Listeria monocytogenes penetrates further into the CNS via the ventricles and spreads through the perivascular spaces and thus forms abscesses. Extensive efferocytosis observed is believed to be used by L. monocytogenes for cell-to-cell spread. Furthermore, we studied animal models of bacterial meningitis to determine if these mimic meningitis in humans

Histopathology of bacterial meningitis: Snapshots of the brain

Bacterial meningitis shows histopathological characteristics that are specific to each causative agent. Identifying these specific characteristics is important because it adds to the knowledge about the pathophysiology of tissue damage by the various causative agents. This could possibly lead to the development of new, more effective treatments. We studied 31 cases of pneumococcal meningitis and the specific histopathological characteristics were described, namely: inflammation of the medium and large arteries, intraparenchymal bleeding, cerebritis, thrombosis, and infarctions. Of these characteristics, inflammation of medium and large arteries is not only practically universally present, but is also clearly associated with thrombosis and infarctions. This suggests that vascular damage plays a key role in the pathophysiology of brain damage in pneumococcal meningitis. The study of 4 autopsy cases of pneumococcal meningitis with catastrophic cebrovascular complications after initially successful recovery showed that its etiology is multifactorial with vascular inflammation, thromboembolism in the large arteries and infectious intracranial aneurysms. The observation that Streptococcus pneumoniae could be detected intra- and extracellularly (individually or in groups) in patients treated with antibiotics (up to 35 days in length) is striking. We studied the histopathological characteristics of listeria meningitis with the same methodology and the observations show that Listeria monocytogenes penetrates further into the CNS via the ventricles and spreads through the perivascular spaces and thus forms abscesses. Extensive efferocytosis observed is believed to be used by L. monocytogenes for cell-to-cell spread. Furthermore, we studied animal models of bacterial meningitis to determine if these mimic meningitis in humans

Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path)

Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non-dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path)

Microglial Activation After Systemic Stimulation With Lipopolysaccharide and Escherichia coil

Intensive Car

Proteomic profiling of the spinal cord in ALS: decreased ATP5D levels suggest synaptic dysfunction in ALS pathogenesis

Background: We aimed to gain new insights into the pathogenesis of sporadic ALS (sALS) through a comprehensive proteomic analysis. Methods: Protein profiles of the anterior and posterior horn in post-mortem spinal cord samples of 10 ALS patients and 10 controls were analysed using 2D-differential gel electrophoresis. The identified protein spots with statistically significant level changes and a spot ratio >2.0 were analysed by LC-MS/MS. Results: In the posterior horn only 3 proteins were differentially expressed. In the anterior horn, 16 proteins with increased levels and 2 proteins with decreased levels were identified in ALS compared to controls. The identified proteins were involved in mitochondrial metabolism, calcium homeostasis, protein metabolism, glutathione homeostasis, protein transport and snRN

Measurement of diffractive photoproduction of vector mesons at large momentum transfer at HERA

Elastic and proton-dissociative photoproduction of rho /sup 0/, phi and J/ psi vector mesons ( gamma p to Vp, gamma p to VN, respectively) have been measured in e/sup +/p interactions at HERA up to -t=3 GeV/sup 2/, where t is the four-momentum transfer squared at the photon-vector-meson vertex. The analysis is based on a data sample in which photoproduction reactions were tagged by detection of the scattered positron in a special-purpose calorimeter. This limits the photon virtuality, Q/sup 2/, to values less than 0.01 GeV/sup 2/, and selects a gamma p average center-of-mass energy of [W]=94 GeV. Results for the differential cross sections, d sigma /dt, for rho /sup 0/, phi and J/ psi mesons are presented and compared to the results of recent QCD calculations. Results are also presented for the t-dependence of the pion-pair invariant-mass distribution in the rho /sup 0/ mass region and of the spin-density matrix elements determined from the decay-angle distributions. The Pomeron trajectory has been derived from measurements of the W dependence of the elastic differential cross sections d sigma /dt for both rho /sup 0/ and phi mesons

Multiplicity moments in deep inelastic scattering at HERA

Multiplicity moments of charged particles in deep inelastic e(+) p scattering have been measured with the ZEUS detector at HERA using an integrated luminosity of 38.3 pb(-1). The moments for Q(2) gt 1000 GeV2 were studied in the current region of the Breit frame. The evolution of the moments was investigated as a function of restricted regions in polar angle and, for the first time, both in the transverse momentum and in absolute momentum of final-state particles. Analytic perturbative QCD predictions in conjunction with the hypothesis of Local Parton- Hadron Duality (LPHD) reproduce the trends of the moments in polar-angle regions, although some discrepancies are observed. For the moments restricted either in transverse or absolute momentum, the analytic results combined with the LPHD hypothesis show considerable deviations from the measurements. The study indicates a large influence of the hadronisation stage on the multiplicity distributions in the restricted phase-space regions studied here, which is inconsistent with the expectations of the LPHD hypothesis