332 research outputs found
Transgenic rat with overproduction of ubiquitous angiotensin-(1-7) presents neuroprotection in a model of ischemia and reperfusion
Recent studies showed that angiotensin-(1-7) has cerebroprotective actions in stroke. In the present study, we aim to test whether tissue overexpression of Angiotensin-(1-7), mainly in the brain provides neuroprotection in a model of ischemia/reperfusion by bilateral common carotid arteries occlusion/reperfusion (BCCAo/R). Evaluation of neurological deficit scores and bilateral asymmetry test (BAT) were performed seven days after transient BCCAo/R in transgenic rats (TG-7371) overexpressing Angiotensin-(1-7) and Sprague-Dawley (SD) rats. To assess blood-brain barrier (BBB) permeability Evans blue dye (EB) was intravenously injected. Cytokine levels were quantified in the whole brain through Elisa assay and oxidative stress was measured 7 days after ischemia. The expression of AT(1) and Mas receptors and inducible nitric oxide synthase (iNOS) was evaluated by RT-PCR. Neurological deficits were observed in both SD-BCCAo/R and TG-BCCAo/R, contrasting to sham-operated groups. However, TG-BCCAo/R showed a significant lower neurological score and latency in BAT when compared with SD-BCCAo/R. BBB integrity in TG-BCCAo/R was improved, since these animals showed lower extravasation of EB than SD-BCCAo/R. Interestingly, TG-BCCAo/R presented lower levels of pro-inflammatory cytokines when compared to SD-BCCAo/R. Levels of IL-10 were higher in SD-BCCAo/R than in SD control and even higher in TG-BCCAo/R. TG-BCCAo/R animals presented decreased levels of TBARS and increase in SOD activity and GSH levels when compared to SD sham rats. RT-PCR results showed higher levels of AT(1) receptor and iNOS in SD-BCCAo/R compared to TG-BCCAo/R, but no difference was observed for Mas receptor. The present study shows that lifetime increase in cerebral expression of an Ang-(1-7)-producing fusion protein induces neuroprotection in experimental global cerebral ischemia and reperfusion, reassuring that, pharmacological strategies leading to increase in Ang-(1-7) can be an additional tool for stroke therapy
Polyphenols journey through blood-brain barrier towards neuronal protection
Age-related complications such as neurodegenerative disorders are increasing and remain cureless.
The possibility of altering the progression or the development of these multifactorial diseases through
diet is an emerging and attractive approach with increasing experimental support. We examined
the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to
infuence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies
across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for
diferential transport, likely related to chemical structure. Moreover, endothelial metabolism of these
phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies.
Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and
infammatory injuries and this attenuation of neuroinfammation was achieved via modulation of
NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary
(poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated infammation and
exert neuroprotective efects, with potential for alleviation of neurodegenerative diseases.info:eu-repo/semantics/publishedVersio
The exposure of the hybrid detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays.
It consists of a surface array to measure secondary particles at ground level
and a fluorescence detector to measure the development of air showers in the
atmosphere above the array. The "hybrid" detection mode combines the
information from the two subsystems. We describe the determination of the
hybrid exposure for events observed by the fluorescence telescopes in
coincidence with at least one water-Cherenkov detector of the surface array. A
detailed knowledge of the time dependence of the detection operations is
crucial for an accurate evaluation of the exposure. We discuss the relevance of
monitoring data collected during operations, such as the status of the
fluorescence detector, background light and atmospheric conditions, that are
used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic
Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory
Atmospheric parameters, such as pressure (P), temperature (T) and density,
affect the development of extensive air showers initiated by energetic cosmic
rays. We have studied the impact of atmospheric variations on extensive air
showers by means of the surface detector of the Pierre Auger Observatory. The
rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find
that the observed behaviour is explained by a model including the effects
associated with the variations of pressure and density. The former affects the
longitudinal development of air showers while the latter influences the Moliere
radius and hence the lateral distribution of the shower particles. The model is
validated with full simulations of extensive air showers using atmospheric
profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle
Physic
The Fluorescence Detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a hybrid detector for ultra-high energy
cosmic rays. It combines a surface array to measure secondary particles at
ground level together with a fluorescence detector to measure the development
of air showers in the atmosphere above the array. The fluorescence detector
comprises 24 large telescopes specialized for measuring the nitrogen
fluorescence caused by charged particles of cosmic ray air showers. In this
paper we describe the components of the fluorescence detector including its
optical system, the design of the camera, the electronics, and the systems for
relative and absolute calibration. We also discuss the operation and the
monitoring of the detector. Finally, we evaluate the detector performance and
precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics
Research Section
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