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Lower doses of isoflurane treatment has no beneficial effects in a rat model of intracerebral hemorrhage
Background: Intracerebral hemorrhage is a subtype of stroke that has a poor prognosis without an adequate therapy. Recently, the use of anesthetics such as isoflurane has been shown to be protective after cerebral ischemia. However, the potential therapeutic effect of isoflurane after intracerebral hemorrhage (ICH) has not been fully explored. Results: In this study, male Sprague–Dawley rats (SD) were subjected to ICH and randomized into controls and 1.2% or 1.5% isoflurane posttreatment groups. Brain water content, neurological outcomes and matrix metalloproteinase-2 and -9 (MMP2-MMP9) plasma levels were quantified at 24 hours. Isoflurane treatment did not reduce brain edema compared with controls in any of the applied isoflurane concentrations. Moreover, consistent with this lack of effect on brain edema, isoflurane posttreatment did not affect neurological outcomes in any of the tests used. Plasma MMP levels did not change. Conclusion: Our data suggested that there is no neuroprotection after isoflurane posttreatment in a rat model of ICH
Toxicosis from Range Lupine Ingestion in a Research Herd of Rafter 7 Merino Sheep
An outbreak of lupine alkaloid neurotoxicosis and death occurred in sheep grazed on rangeland areas of the Nevada Great Basin during the summer of 2023. Overall, 97 sheep died despite veterinary supportive care. Lupinus argenteus var. utahensis was implicated as the causative plant with high levels of lupanine (11.5 µg/mg) and spartiene (13.7 µg/mg) in collected and archived samples. Previous reports of sheep deaths due to lupine ingestion have not been recorded in this region. An increased abundance of the number plants producing seed pods having a high alkaloid content may have been associated with abnormally elevated levels of precipitation in the months leading to the event
Fibrin regulates neutrophil migration in response to interleukin 8, leukotriene B4, tumor necrosis factor, and formyl-methionyl-leucyl-phenylalanine
We have examined the capacity of four different chemoattractants/cytokines to promote directed migration of polymorphonuclear leukocytes (PMN) through three-dimensional gels composed of extracellular matrix proteins. About 20% of PMN migrated through fibrin gels and plasma clots in response to a gradient of interleukin 8 (IL-8) or leukotriene B4 (LTB4). In contrast, < 0.3% of PMN migrated through fibrin gels in response to a gradient of tumor necrosis factor alpha (TNF) or formyl-methionyl-leucyl-phenylalanine (FMLP). All four chemoattractants stimulated PMN to migrate through gels composed of collagen IV or of basement membrane proteins (Matrigel), or through filters to which fibronectin or fibrinogen had been adsorbed. PMN stimulated with TNF or FMLP adhered and formed zones of close apposition to fibrin, as measured by the exclusion of a 10-kD rhodamine-polyethylene glycol probe from the contact zones between PMN and the underlying fibrin gel. By this measure, IL-8- or LTB4-treated PMN adhered loosely to fibrin, since 10 kD rhodamine-polyethylene glycol permeated into the contact zones between these cells and the underlying fibrin gel. PMN stimulated with FMLP and IL-8, or FMLP and LTB4, exhibited very little migration through fibrin gels, and three times as many of these cells excluded 10 kD rhodamine-polyethylene glycol from their zones of contact with fibrin as PMN stimulated with IL-8 or LTB4 alone. These results show that PMN chemotaxis is regulated by both the nature of the chemoattractant and the composition of the extracellular matrix; they suggest that certain combinations of chemoattractants and matrix proteins may limit leukocyte movements and promote their localization in specific tissues in vivo
Diurnal Differences in Immune Response in Brain, Blood and Spleen After Focal Cerebral Ischemia in Mice.
BACKGROUND
The immune response to acute cerebral ischemia is a major factor in stroke pathobiology. Circadian biology modulates some aspects of immune response. The goal of this study is to compare key parameters of immune response during the active/awake phase versus inactive/sleep phase in a mouse model of transient focal cerebral ischemia.
METHODS
Mice were housed in normal or reversed light cycle rooms for 3 weeks, and then they were blindly subjected to transient focal cerebral ischemia. Flow cytometry was used to examine immune responses in blood, spleen, and brain at 3 days after ischemic onset.
RESULTS
In blood, there were higher levels of circulating T cells in mice subjected to focal ischemia during zeitgeber time (ZT)1-3 (inactive or sleep phase) versus ZT13-15 mice (active or awake phase). In the spleen, organ weight and immune cell numbers were lower in ZT1-3 versus ZT13-15 mice. Consistent with these results, there was an increased infiltration of activated T cells into brain at ZT1-3 compared with ZT13-15.
CONCLUSIONS
This proof-of-concept study indicates that there are significant diurnal effects on the immune response after focal cerebral ischemia in mice. Hence, therapeutic strategies focused on immune targets should be reassessed to account for the effects of diurnal rhythms and circadian biology in nocturnal rodent models of stroke.Supported in part by the Rappaport Foundation and Leducq Foundation. The
authors thank all team members of the MGH animal facility for help with light
schedule switching.S
Exponential Distribution of Locomotion Activity in Cell Cultures
In vitro velocities of several cell types have been measured using computer
controlled video microscopy, which allowed to record the cells' trajectories
over several days. On the basis of our large data sets we show that the
locomotion activity displays a universal exponential distribution. Thus, motion
resulting from complex cellular processes can be well described by an
unexpected, but very simple distribution function. A simple phenomenological
model based on the interaction of various cellular processes and finite ATP
production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure
A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region
The coincidence cross-section and the interference structure function, R_LT,
were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and
central momentum transfer of q=400 MeV/c. The measurement was at an opening
angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to
65 MeV. The R_LT structure function is found to be consistent with zero for E_m
> 50 MeV, confirming an earlier study which indicated that R_L vanishes in this
region. The integrated strengths of the p- and s-shell are compared with a
Distorted Wave Impulse Approximation calculation. The s-shell strength and
shape are compared with a Hartree Fock-Random Phase Approximation calculation.
The DWIA calculation overestimates the cross sections for p- and s-shell proton
knockout as expected, but surprisingly agrees with the extracted R_LT value for
both shells. The HF-RPA calculation describes the data more consistently, which
may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.
Relativistic effects and two-body currents in using out-of-plane detection
Measurements of the reaction were performed
using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator
and with the out-of-plane magnetic spectrometers (OOPS). The
longitudinal-transverse, and , and the
transverse-transverse, , interference responses at a missing momentum
of 210 MeV/c were simultaneously extracted in the dip region at Q=0.15
(GeV/c). On comparison to models of deuteron electrodisintegration, the
data clearly reveal strong effects of relativity and final-state interactions,
and the importance of the two-body meson-exchange currents and isobar
configurations. We demonstrate that these effects can be disentangled and
studied by extracting the interference response functions using the novel
out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio
Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke
Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties
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