Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice

Background Recent data indicates that cerebrospinal fluid (CSF) dynamics are disturbed after stroke. Our lab has previously shown that intracranial pressure rises dramatically 24 h after experimental stroke and that this reduces blood flow to ischaemic tissue. CSF outflow resistance is increased at this time point. We hypothesised that reduced transit of CSF through brain parenchyma and reduced outflow of CSF via the cribriform plate at 24 h after stroke may contribute to the previously identified post-stroke intracranial pressure elevation. Methods Using a photothrombotic permanent occlusion model of stroke in C57BL/6 adult male mice, we examined the movement of an intracisternally infused 0.5% Texas Red dextran throughout the brain and measured tracer efflux into the nasal mucosa via the cribriform plate at 24 h or two weeks after stroke. Brain tissue and nasal mucosa were collected ex vivo and imaged using fluorescent microscopy to determine the change in CSF tracer intensity in these tissues. Results At 24 h after stroke, we found that CSF tracer load was significantly reduced in brain tissue from stroke animals in both the ipsilateral and contralateral hemispheres when compared to sham. CSF tracer load was also reduced in the lateral region of the ipsilateral hemisphere when compared to the contralateral hemisphere in stroke brains. In addition, we identified an 81% reduction in CSF tracer load in the nasal mucosa in stroke animals compared to sham. These alterations to the movement of CSF-borne tracer were not present at two weeks after stroke. Conclusions Our data indicates that influx of CSF into the brain tissue and efflux via the cribriform plate are reduced 24 h after stroke. This may contribute to reported increases in intracranial pressure at 24 h after stroke and thus worsen stroke outcomes.K. E. Warren, K. G. Coupland, R. J. Hood, L. Kang, F. R. Walker, and N. J. Sprat

Shape and blocking effects on odd-even mass differences and rotational motion of nuclei

Nuclear shapes and odd-nucleon blockings strongly influence the odd-even differences of nuclear masses. When such effects are taken into account, the determination of the pairing strength is modified resulting in larger pair gaps. The modified pairing strength leads to an improved self-consistent description of moments of inertia and backbending frequencies, with no additional parameters.Comment: 7 pages, 3 figures, subm to PR

The distance to the Sgr dwarf spheroidal galaxy from the Red Giant Branch Tip

We derived the distance to the central region of the Sagittarius dwarf spheroidal galaxy from the Red Giant Branch Tip. The obtained distance modulus is $(m-M)_0=17.10\pm0.15$, corresponding to a heliocentric distance $D=26.30\pm1.8$ Kpc. This estimate is in good agreement with the distance obtained from RR Lyrae stars of the globular cluster M~54, located in the core of the Sgr galaxy, once the most accurate estimate of the cluster metallicity and the most recent calibration of the $M_V(RRLy) vs.[Fe/H]$ relation are adopted.Comment: 6 pages, 5 figure, Accepted for publication in MNRA

Early treatment with minocycline following stroke in rats improves functional recovery and differentially modifies responses of peri-infarct microglia and astrocytes

BACKGROUND: Altered neuronal connectivity in peri-infarct tissue is an important contributor to both the spontaneous recovery of neurological function that commonly develops after stroke and improvements in recovery that have been induced by experimental treatments in animal models. Microglia and astrocytes are primary determinants of the environment in peri-infarct tissue and hence strongly influence the potential for neuronal plasticity. However, the specific roles of these cells and the timing of critical changes in their function are not well understood. Minocycline can protect against ischemic damage and promote recovery. These effects are usually attributed, at least partially, to the ability of this drug to suppress microglial activation. This study tested the ability of minocycline treatment early after stroke to modify reactive responses in microglia and astrocytes and improve recovery. METHODS: Stroke was induced by photothrombosis in the forelimb sensorimotor cortex of Sprague-Dawley rats. Minocycline was administered for 2 days after stroke induction and the effects on forelimb function assessed up to 28 days. The responses of peri-infarct Iba1-positive cells and astrocytes were evaluated using immunohistochemistry and Western blots. RESULTS: Initial characterization showed that the numbers of Iba1-positive microglia and macrophages decreased in peri-infarct tissue at 24 h then increased markedly over the next few days. Morphological changes characteristic of activation were readily apparent by 3 h and increased by 24 h. Minocycline treatment improved the rate of recovery of motor function as measured by a forelimb placing test but did not alter infarct volume. At 3 days, there were only minor effects on core features of peri-infarct microglial reactivity including the morphological changes and increased density of Iba1-positive cells. The treatment caused a decrease of 57% in the small subpopulation of cells that expressed CD68, a marker of phagocytosis. At 7 days, the expression of glial fibrillary acidic protein and vimentin was markedly increased by minocycline treatment, indicating enhanced reactive astrogliosis. CONCLUSIONS: Early post-stroke treatment with minocycline improved recovery but had little effect on key features of microglial activation. Both the decrease in CD68-positive cells and the increased activation of astrogliosis could influence neuronal plasticity and contribute to the improved recovery.Wai Ping Yew, Natalia D. Djukic, Jaya S. P. Jayaseelan, Frederick R. Walker, Karl A. A. Roos, Timothy K. Chataway, Hakan Muyderman and Neil R. Sim

What do stroke survivors' value about participating in research and what are the most important research problems related to stroke or transient ischemic attack (TIA)? A survey

Background: Recruitment to stroke clinical trials is challenging, but consumer registers can facilitate participation. Researchers need to understand the key factors that facilitate trial involvement and improve consumer partnerships to identify what research topics important to stroke and transient ischemic attack (TIA) survivors and their carers. We aimed to examine i) the experience of being involved in a stroke research register, and ii) the priorities for stroke research from the perspective of stroke survivors. Methods: Online and paper-based surveys were sent directly to members of a stroke register and disseminated online. Multiple choice questions were reported as counts and percentages and open-ended questions were thematically analysed using Braun and Clarke’s 6-stage process. Results: Of 445 survey respondents, 154 (38%) were a member of the Stroke Research Register. The most frequently reported reason for research participation was to help others in the future. Respondents reported they were less likely to take part in research if the research question was not relevant to them, if transport was an issue, or because they lacked time. The most important research problems reported were targeting specific impairments including recovery of movement, fatigue, and aphasia, improvement of mental health services, and increased support for carers. Conclusions: Recruitment to trials may be improved by research registers if an inclusive research culture is fostered, in which consumers feel valued as members of a community, have direct and timely access to research findings and the opportunity to be meaningfully involved in research around the problems that consumers find most important.Ishanka Weerasekara, Jasmine Baye, Meredith Burke, Gary Crowfoot, Gillian Mason, Rachael Peak, Dawn Simpson, Frederick Rohan Walker, Michael Nilsson, Michael Pollack, and Coralie Englis

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Hereditary thrombophilia and fetal loss: a prospective follow-up study

Background: As the placental vessels are dependent on the normal balance of procoagulant and anticoagulant mechanisms, inherited thrombophilia may be associated with fetal loss. Objectives: We performed a prospective study to investigate the relation between inherited thrombophilia and fetal loss, and the influence of thromboprophylaxis on pregnancy outcome. Patients and methods: Women were enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). These included women with factor (F)V Leiden or a deficiency of antithrombin, protein C or protein S. Controls were partners or acquaintances of thrombophilic individuals. A total of 191 women (131 with thrombophilia, 60 controls) had a pregnancy outcome during prospective follow-up. Risk of fetal loss and effect of thromboprophylaxis were estimated by frequency calculation and Cox regression modelling. Results: The risk of fetal loss appeared slightly increased in women with thrombophilia without a previous history of fetal loss who did not use any anticoagulants during pregnancy (7/39 vs. 7/51; relative risk 1.4; 95% confidence interval 0.4, 4.7). Per type of defect the relative risk varied only minimally from 1.4 for FV Leiden to 1.6 for antithrombin deficiency compared with control women. Prophylactic anticoagulant treatment during pregnancy in 83 women with thrombophilia differed greatly in type, dose and duration, precluding solid conclusions on the effect of thromboprophylaxis on fetal loss. No clear benefit of anticoagulant prophylaxis was apparent. Conclusions: Women with thrombophilia appear to have an increased risk of fetal loss, although the likelihood of a positive outcome is high in both women with thrombophilia and in controls