CSF Secretion Is Not Altered by NKCC1 Nor TRPV4 Antagonism in Healthy Rats

Background: Cerebrospinal fluid (CSF) secretion can be targeted to reduce elevated intracranial pressure (ICP). Sodium-potassium-chloride cotransporter 1 (NKCC1) antagonism is used clinically. However, supporting evidence is limited. The transient receptor potential vanilloid-4 (TRPV4) channel may also regulate CSF secretion and ICP elevation. We investigated whether antagonism of these proteins reduces CSF secretion. Methods: We quantified CSF secretion rates in male Wistar rats. The cerebral aqueduct was blocked with viscous mineral oil, and a lateral ventricle was cannulated. Secretion rate was measured at baseline and after antagonist administration. Acetazolamide was administered as a positive control to confirm changes in CSF secretion rates. Results: Neither NKCC1, nor TRPV4 antagonism altered CSF secretion rate from baseline, n = 3, t(2) = 1.14, p = 0.37, and n = 4, t(3) = 0.58, p = 0.6, respectively. Acetazolamide reduced CSF secretion by ~50% across all groups, n = 7, t(6) = 4.294, p = 0.005. Conclusions: Acute antagonism of NKCC1 and TRPV4 proteins at the choroid plexus does not reduce CSF secretion in healthy rats. Further investigation of protein changes and antagonism should be explored in neurological disease where increased CSF secretion and ICP are observed before discounting the therapeutic potential of protein antagonism at these sites

Decreased Intracranial Pressure Elevation and Cerebrospinal Fluid Outflow Resistance: A Potential Mechanism of Hypothermia Cerebroprotection Following Experimental Stroke

Background: Elevated intracranial pressure (ICP) occurs 18–24 h after ischaemic stroke and is implicated as a potential cause of early neurological deterioration. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. Ultra-short duration hypothermia prevents ICP elevation 24 h post-stroke in rats. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Methods: Transient middle cerebral artery occlusion was performed, followed by gradual cooling to 33 °C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 °C prevented ICP elevation 18 h post-stroke (hypothermia ∆ICP = 0.8 ± 3.6 mmHg vs. normothermia ∆ICP = 4.4 ± 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 ± 21.3 mm(3) vs. normothermia = 108.1 ± 17.8 mm(3); p = 0.01). Hypothermia to 33 °C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 ± 0.36 mmHg/µL/min vs. 1.07 ± 0.99 mmHg/µL/min, p = 0.06). Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment

ASTER, a multinational Earth observing concept

The Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is a facility instrument selected for launch in 1998 on the first in a series of spacecraft for NASA's Earth Observing System (EOS). The ASTER instrument is being sponsored and built in Japan. It is a three telescope, high spatial resolution imaging instrument with 15 spectral bands covering the visible through to the thermal infrared. It will play a significant role within EOS providing geological, biological, land hydrological information necessary for intense study of the Earth. The operational capabilities for ASTER, including the necessary interfaces and operational collaborations between the US and Japanese participants, are under development. EOS operations are the responsibility of the EOS Project at NASA's Goddard Space Flight Center (GSFC). Although the primary EOS control center is at GSFC, the ASTER control facility will be in Japan. Other aspects of ASTER are discussed

Altered Cerebrospinal Fluid Clearance and Increased Intracranial Pressure in Rats 18 h After Experimental Cortical Ischaemia

Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow

Ultra-Short Duration Hypothermia Prevents Intracranial Pressure Elevation Following Ischaemic Stroke in Rats

There is a transient increase in intracranial pressure (ICP) 18–24 h after ischaemic stroke in rats, which is prevented by short-duration hypothermia using rapid cooling methods. Clinical trials of long-duration hypothermia have been limited by feasibility and associated complications, which may be avoided by short-duration cooling. Animal studies have cooled faster than is achievable in patients. We aimed to determine whether gradual cooling at a rate of 2°C/h to 33°C or 1°C/h to 34.5°C, with a 30 min duration at target temperatures, prevented ICP elevation and reduced infarct volume in rats. Transient middle cerebral artery occlusion was performed, followed by gradual cooling to target temperature. Hypothermia to 33°C prevented significant ICP elevation (hypothermia ΔICP = 1.56 ± 2.26 mmHg vs normothermia ΔICP = 8.93 ± 4.82 mmHg; p = 0.02) and reduced infarct volume (hypothermia = 46.4 ± 12.3 mm3 vs normothermia = 85.0 ± 17.5 mm3; p = 0.01). Hypothermia to 34.5°C did not significantly prevent ICP elevation or reduce infarct volume. We showed that gradual cooling to 33°C, at cooling rates achievable in patients, had the same ICP preventative effect as traditional rapid cooling methods. This suggests that this paradigm could be translated to prevent delayed ICP rise in stroke patients

dOCRL maintains immune cell quiescence in Drosophila by regulating endosomal traffic

Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system. Among many cell biological defects that we identified in docrl mutant hemocytes, we pinpointed the cause of innate immune cell activation to reduced Rab11-dependent recycling traffic and concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT, and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll ligand Spåtzle. Thus, docrl regulation of endosomal traffic maintains hemocytes in a poised, but quiescent state, suggesting mechanisms by which endosomal misregulation of signaling may contribute to symptoms of Lowe syndrome

Comparing Effects of Nutrients on Algal Biomass in Streams in Two Regions with Different Disturbance Regimes and with Applications for Developing Nutrient Criteria

Responses of stream algal biomass to nutrient enrichment were studied in two regions where differences in hydrologic variability cause great differences in herbivory. Around northwestern Kentucky (KY) hydrologic variability constrains invertebrate biomass and their effects on algae, but hydrologic stability in Michigan (MI) streams permits accrual of high herbivore densities and herbivory of benthic algae. Multiple indicators of algal biomass and nutrient availability were measured in 104 streams with repeated sampling at each site over a 2−month period. Many measures of algal biomass and nutrient availability were positively correlated in both regions, however the amount of variation explained varied with measures of biomass and nutrient concentration and with region. Indicators of diatom biomass were higher in KY than MI, but were not related to nutrient concentrations in either region. Chl   a and % area of substratum covered by Cladophora were positively correlated to nutrient concentrations in both regions. Cladophora responded significantly more to nutrients in MI than KY. Total phosphorus (TP) and total nitrogen (TN) explained similar amounts of variation in algal biomass, and not significantly more variation in biomass than dissolved nutrient concentrations. Low N:P ratios in the benthic algae indicated N as well as P may be limiting their accrual. Most observed responses in benthic algal biomass occurred in nutrient concentrations between 10 and 30 μg TP  l −1 and between 400 and 1000 μg TN l −1 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42905/1/10750_2005_Article_1611.pd

Fit-for-work: mental health and alcohol indicators in male-dominated industries

Purpose: Risky alcohol use can reduce productivity at work and impact employees’ mental health and wellbeing. Several risk factors converge in male-dominated industries, which can increase risky drinking and deteriorate mental health. This paper aims to explore the prevalence of risky drinking and psychological distress in a male-dominated industry compared with that in the general population. Design/methodology/approach: Data were collected from four manufacturing sites in Australia. In total, 450 workers were invited to participate in a survey that measured drinking behaviours using AUDIT-C and psychological distress using the K10, along with demographics including age, gender, job role and ethnicity. The observed outcome measures were compared with general population data available through publicly available data sets. Findings: Surveys were returned by 341 employees, of which 319 completed AUDIT-C. AUDIT-C and K10 scores were significantly correlated (R = 0.31, p \u3c 0.0001). Hazardous drinking was more prevalent among workers than in Australian general population (66.1% vs 23.6%). Binge drinking was greater among workers than in the general population (25.4% vs 26.5%). The difference was higher among female workers than among male workers (35.1% vs 10.8%). Originality/value: The findings of this study show a significantly greater risk of alcohol-related harm among workers in male-dominated industries compared with that in the general population. This risk is more pronounced among women, who also experienced greater rates of moderate and high psychological distress compared with those experienced by the general population. A fitness-for-work approach is proposed to minimise alcohol-related harm among workers in male-dominated industries. Moreover, male-dominated industries are proposed to consider the interconnectivity of other workplace health and safety factors