β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices

<p>Abstract</p> <p>Background</p> <p>Inflammation acting in synergy with brain ischemia aggravates perinatal ischemic brain damage. The sensitizing effect of pro-inflammatory exposure prior to hypoxia is dependent on signaling by TNF-α through TNF receptor (TNFR) 1. Adrenoceptor (AR) activation is known to modulate the immune response and synaptic transmission. The possible protective effect of <inline-formula><m:math xmlns:m="http://www.w3.org/1998/Math/MathML" name="1742-2094-7-94-i1"><m:mover accent="true"><m:mi>α</m:mi><m:mo>˜</m:mo></m:mover></m:math></inline-formula> and <inline-formula><m:math xmlns:m="http://www.w3.org/1998/Math/MathML" name="1742-2094-7-94-i2"><m:mover accent="true"><m:mi>β</m:mi><m:mo>˜</m:mo></m:mover></m:math></inline-formula>AR activation against neuronal damage caused by tissue ischemia and inflammation, acting in concert, was evaluated in murine hippocampal organotypic slices treated with lipopolysaccharide (LPS) and subsequently subjected to oxygen-glucose deprivation (OGD).</p> <p>Method</p> <p>Hippocampal slices from mice were obtained at P6, and were grown <it>in vitro </it>for 9 days on nitrocellulose membranes. Slices were treated with β1(dobutamine)-, β2(terbutaline)-, α1(phenylephrine)- and α2(clonidine)-AR agonists (5 and 50 μM, respectively) during LPS (1 μg/mL, 24 h) -exposure followed by exposure to OGD (15 min) in a hypoxic chamber. Cell death in the slice CA1 region was assessed by propidium iodide staining of dead cells.</p> <p>Results</p> <p>Exposure to LPS + OGD caused extensive cell death from 4 up to 48 h after reoxygenation. Co-incubation with β1-agonist (50 μM) during LPS exposure before OGD conferred complete protection from cell death (P < 0.001) whereas the β2-agonist (50 μM) was partially protective (p < 0.01). Phenylephrine was weakly protective while no protection was attained by clonidine. Exposure to both β1- and β2-agonist during LPS exposure decreased the levels of secreted TNF-α, IL-6 and monocyte chemoattractant protein-1 and prevented microglia activation in the slices. Dobutamine remained neuroprotective in slices exposed to pure OGD as well as in TNFR1^-/-and TNFR2^-/-slices exposed to LPS followed by OGD.</p> <p>Conclusions</p> <p>Our data demonstrate that activation of both β1- and β2-receptors is neuroprotective and may offer mechanistic insights valuable for development of neuro-protective strategies in neonates.</p

An experimental survey of the production of alpha decaying heavy elements in the reactions of 238^{238}U +232^{232}Th at 7.5-6.1 MeV/nucleon

The production of alpha particle decaying heavy nuclei in reactions of 7.5-6.1 MeV/nucleon $^{238}$U +$^{232}$Th has been explored using an in-beam detection array composed of YAP scintillators and gas ionization chamber-Si telescopes. Comparisons of alpha energies and half-lives for the observed products with those of the previously known isotopes and with theoretically predicted values indicate the observation of a number of previously unreported alpha emitters. Alpha particle decay energies reaching as high as 12 MeV are observed. Many of these are expected to be from decay of previously unseen relatively neutron rich products. While the contributions of isomeric states require further exploration and specific isotope identifications need to be made, the production of heavy isotopes with quite high atomic numbers is suggested by the data.Comment: 12 pages, 12 figure

Elements Discrimination in the Study of Super-Heavy Elements using an Ionization Chamber

Dedicated ionization chamber was built and installed to measure the energy loss of very heavy nuclei at 2.7 MeV/u produced in fusion reactions in inverse kinematics (beam of 208Pb). After going through the ionization chamber, products of reactions on 12C, 18O targets are implanted in a Si detector. Their identification through their alpha decay chain is ambiguous when their half-life is short. After calibration with Pb and Th nuclei, the ionization chamber signal allowed us to resolve these ambiguities. In the search for rare super-heavy nuclei produced in fusion reactions in inverse or symmetric kinematics, such a chamber will provide direct information on the nuclear charge of each implanted nucleus.Comment: submitted to NIMA, 10 pages+4 figures, Latex, uses elsart.cls and grahpic

Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke

Understanding circuit-level manipulations that affect the brain\u27s capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems- and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received chronic optogenetic excitation of right S1FP over the course of 4 weeks. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of stimulus-evoked activity in the unaffected limb. This maneuver also prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited transcriptional changes in several genes relevant for recovery. Our results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of cortical activity and several neuroplasticity-related genes after stroke, and highlight the importance of site selection for targeted therapeutic interventions after focal ischemia

Pseudorapidity distributions of charged particles from Au+Au collisions at the maximum RHIC energy, Sqrt(s_NN) = 200 GeV

We present charged particle densities as a function of pseudorapidity and collision centrality for the 197Au+197Au reaction at Sqrt{s_NN}=200 GeV. For the 5% most central events we obtain dN_ch/deta(eta=0) = 625 +/- 55 and N_ch(-4.7<= eta <= 4.7) = 4630+-370, i.e. 14% and 21% increases, respectively, relative to Sqrt{s_NN}=130 GeV collisions. Charged-particle production per pair of participant nucleons is found to increase from peripheral to central collisions around mid-rapidity. These results constrain current models of particle production at the highest RHIC energy.Comment: 4 pages, 5 figures; fixed fig. 5 caption; revised text and figures to show corrected calculation of and ; final version accepted for publicatio

Charged particle densities from Au+Au collisions at sqrt{s_{NN}}=130 GeV

We present charged particle densities as a function of pseudorapidity and collision centrality for the 197Au+197Au reaction at sqrt{s_{NN}}=130 GeV. An integral charged particle multiplicity of 3860+/-300 is found for the 5% most central events within the pseudorapidity range -4.7 <= eta <= 4.7. At mid-rapidity an enhancement in the particle yields per participant nucleon pair is observed for central events. Near to the beam rapidity, a scaling of the particle yields consistent with the ``limiting fragmentation'' picture is observed. Our results are compared to other recent experimental and theoretical discussions of charged particle densities in ultra-relativistic heavy-ion collisions.Comment: 14 pages, 4 figures; to be published in Phys. Lett.

A novel experimental setup for rare events selection and its potential application to super-heavy elements search

The paper presents a novel instrumentation for rare events selection which was tested in our research of short-lived super-heavy elements production and detection. The instrumentation includes an active catcher multi-elements system and dedicated electronics. The active catcher located in the forward hemisphere is composed of 63 scintillator detection modules. Reaction products of damped collisions between heavy-ion projectiles and heavy-target nuclei are implanted in the fast plastic scintillators of the active catcher modules. The acquisition system trigger delivered by logical branch of the electronics allows to record the reaction products which decay via the alpha-particle emissions or spontaneous fission which take place between beam bursts. One microsecond wave form signal from FADCs contains information on heavy implanted nucleus as well as its decays

Forward and midrapidity like-particle ratios from p+p collisions at sqrt(s)=200 GeV

We present a measurement of pi-\pi+, K-/K+ and pbar/p from p+p collisions at sqrt(s) = 20 0GeV over the rapidity range 0<y<3.4. For pT < 2.0 GeV/c we see no significant transverse momentum dependence of the ratios. All three ratios are independent of rapidity for y ~< 1.5 and then steadily decline from y ~ 1.5 to y ~ 3. The pi-\pi+ ratio is below unity for y > 2.0. The pbar/p ratio is very similar for p+p and 20% central Au+Au collisions at all rapidities. In the fragmentation region the three ratios seem to be independent of beam energy when viewed from the rest frame of one of the protons. Theoretical models based on quark-diquark breaking mechanisms overestimate the pbar/p ratio up to y ~< 3. Including additional mechanisms for baryon number transport such as baryon junctions leads to a better description of the data.Comment: 15 pages, 4 figures, uses elsart.sty. Changes to references and discussion based on referee comments, resubmitted to Phys. Lett.

Gross Properties and Isotopic Phenomena in Spectator Fragmentation

A systematic study of isotopic effects in the break-up of projectile spectators at relativistic energies has been performed with the ALADiN spectrometer at the GSI laboratory. Searching for signals of criticality in the fragment production we have applied the model independent universal fluctuations theory already proposed to track criticality signals in multifragmentation to our data. The fluctuation of the largest fragment charge and of the asymmetry of the two and three largest fragments and their bimodal distribution have also been analysed.Comment: 6 pages, 4 figures, IX International Conference on Nucleus-Nucleus Collisions, Rio de Janeiro, Brazil, August 28 - September 1, 200

Discriminant Analysis and Secondary-Beam Charge Recognition

The discriminant-analysis method has been applied to optimize the exotic-beam charge recognition in a projectile fragmentation experiment. The experiment was carried out at the GSI using the fragment separator (FRS) to produce and select the relativistic secondary beams, and the ALADIN setup to measure their fragmentation products following collisions with Sn target nuclei. The beams of neutron poor isotopes around 124La and 107Sn were selected to study the isospin dependence of the limiting temperature of heavy nuclei by comparing with results for stable 124Sn projectiles. A dedicated detector to measure the projectile charge upstream of the reaction target was not used, and alternative methods had to be developed. The presented method, based on the multivariate discriminant analysis, allowed to increase the efficacy of charge recognition up to about 90%, which was about 20% more than achieved with the simple scalar methods.Comment: 6 pages, 7 eps figures, elsart, submitted to Nucl. Instr. and Meth.