Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

Clostridium perfringens type D epsilon toxin produces a rapid and dose-dependent cytotoxic effect on cerebral microvascular endothelial cells in vitro

Clostridium perfringens type D epsilon toxin (ETX) is responsible for a severe and frequently fatal neurologic disorder in ruminant livestock. Light microscopic, immunohistochemical, and ultrastructural studies have suggested that ETX injury to the cerebral microvasculature, with subsequent severe, generalized vasogenic edema and increased intracranial pressure, is critically important in producing neurologic dysfunction. However, the effect of ETX on brain capillary endothelial cells in vitro has not been examined previously, to our knowledge. We exposed a well-characterized human blood-brain barrier cell line to increasing concentrations of ETX, and demonstrated a direct and dose-dependent endotheliotoxic effect. Our findings are concordant with the primacy of vasculocentric brain lesions in the diagnosis of acute epsilon toxin enterotoxemia in ruminant livestock

First measurement of the Z→μ+μ−Z\rightarrow \mu^+ \mu^- angular coefficients in the forward region of pppp collisions at s=13\sqrt{s}=13 TeV

The first study of the angular distribution of $\mu^+ \mu^-$ pairs produced in the forward rapidity region via the Drell-Yan reaction $pp \rightarrow \gamma^{*}/Z +X \rightarrow l^+ l^- + X$ is presented, using data collected with the LHCb detector at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 5.1 $\rm{fb}^{-1}$. The coefficients of the five leading terms in the angular distribution are determined as a function of the dimuon transverse momentum and rapidity. The results are compared to various theoretical predictions of the $Z$-boson production mechanism and can also be used to probe transverse-momentum-dependent parton distributions within the proton

Branching Fraction Measurements of the Rare Bs0→ϕμ+μ−B^0_s\rightarrow\phi\mu^+\mu^- and Bs0→f2′(1525)μ+μ−B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^- Decays

The branching fraction of the rare $B^0_s\rightarrow\phi\mu^+\mu^-$ decay is measured using data collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 6 fb$^{-1}$, respectively. The branching fraction is reported in intervals of q$^2$, the square of the dimuon invariant mass. In the q$^2$ region between 1.1 and 6.0 GeV$^2$/c$^4$, the measurement is found to lie 3.6 standard deviations below a standard model prediction based on a combination of light cone sum rule and lattice QCD calculations. In addition, the first observation of the rare $B^0_s\rightarrow f_2^\prime(1525)\mu^+\mu^-$ decay is reported with a statistical significance of 9 standard deviations and its branching fraction is determined

Observation of Two New Excited Ξb0\Xi_b^0 States Decaying to Λb0K−π+\Lambda^0_b K^- \pi^+

International audienceTwo narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6  fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22  MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12  MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92)  MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances

Measurement of the charm mixing parameter yCP−yCPKπy_{CP} - y_{CP}^{K\pi} using two-body D0D^0 meson decays

A measurement of the ratios of the effective decay widths of $D^0 \to \pi^-\pi^+$ and $D^0 \to K^-K^+$ decays over that of $D^0 \to K^-\pi^+$ decays is performed with the LHCb experiment using proton-proton collisions at a centre-of-mass energy of $13 \, \mathrm{TeV}$, corresponding to an integrated luminosity of $6 \, \mathrm{fb^{-1}}$. These observables give access to the charm mixing parameters $y_{CP}^{\pi\pi} - y_{CP}^{K\pi}$ and $y_{CP}^{KK} - y_{CP}^{K\pi}$, and are measured as $y_{CP}^{\pi\pi} - y_{CP}^{K\pi} = (6.57 \pm 0.53 \pm 0.16) \times 10^{-3}$, $y_{CP}^{KK} - y_{CP}^{K\pi} = (7.08 \pm 0.30 \pm 0.14) \times 10^{-3}$, where the first uncertainties are statistical and the second systematic. The combination of the two measurements is $y_{CP} - y_{CP}^{K\pi} = (6.96 \pm 0.26 \pm 0.13) \times 10^{-3}$, which is four times more precise than the previous world average

Measurement of the charm mixing parameter yCP−yCPKπy_{CP} - y_{CP}^{K\pi} using two-body D0D^0 meson decays

International audienceA measurement of the ratios of the effective decay widths of D0→π-π+ and D0→K-K+ decays over that of D0→K-π+ decays is performed with the LHCb experiment using proton–proton collisions at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. These observables give access to the charm mixing parameters yCPππ-yCPKπ and yCPKK-yCPKπ, and are measured as yCPππ-yCPKπ=(6.57±0.53±0.16)×10-3, yCPKK-yCPKπ=(7.08±0.30±0.14)×10-3, where the first uncertainties are statistical and the second systematic. The combination of the two measurements is yCP-yCPKπ=(6.96±0.26±0.13)×10-3, which is four times more precise than the previous world average

Measurement of χc1_{c1}(3872) production in proton-proton collisions at s \sqrt{s} = 8 and 13 TeV

International audienceThe production cross-section of the χ$_{c1}$(3872) state relative to the ψ(2S) meson is measured using proton-proton collision data collected with the LHCb experiment at centre-of-mass energies of $\sqrt{s}$ = 8 and 13 TeV, corresponding to integrated luminosities of 2.0 and 5.4 fb$^{−1}$, respectively. The two mesons are reconstructed in the J/ψπ$^{+}$π$^{−}$ final state. The ratios of the prompt and nonprompt χ$_{c1}$(3872) to ψ(2S) production cross-sections are measured as a function of transverse momentum, p$_{T}$, and rapidity, y, of the χ$_{c1}$(3872) and ψ(2S) states, in the kinematic range 4 < p$_{T}$< 20 GeV/c and 2.0 < y < 4.5. The prompt ratio is found to increase with p$_{T}$, independently of y. For the prompt component, the double ratio of the χ$_{c1}$(3872) and ψ(2S) production cross-sections between 13 and 8 TeV is observed to be consistent with unity, independent of p$_{T}$ and centre-of-mass energy.[graphic not available: see fulltext

Search for the rare hadronic decay Bs0→ppˉB_s^0\to p \bar{p}

A search for the rare hadronic decay Bs0→pp¯ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. No evidence of the decay is found and an upper limit on its branching fraction is set at B(Bs0→pp¯)&lt;4.4(5.1)×10-9 at 90% (95%) confidence level; this is currently the world’s best upper limit. The decay mode B0→pp¯ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be B(B0→pp¯)=(1.27±0.15±0.05±0.04)×10-8, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel B0→K+π-. The combination of the two LHCb measurements of the B0→pp¯ branching fraction yields B(B0→pp¯)=(1.27±0.13±0.05±0.03)×10-8.A search for the rare hadronic decay $B_s^0\to p \bar{p}$ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb$^{-1}$. No evidence of the decay is found and an upper limit on its branching fraction is set at ${\cal B}(B_s^0\to p \bar{p}) < 4.4~(5.1) \times 10^{-9}$ at 90% (95%) confidence level; this is currently the world's best upper limit. The decay mode $B^0\to p \bar{p}$ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.15 \pm 0.05 \pm 0.04) \times 10^{-8}$, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel $B^0\to K^+\pi^-$. The combination of the two LHCb measurements of the $B^0\to p \bar{p}$ branching fraction yields ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.13 \pm 0.05 \pm 0.03) \times 10^{-8}$