bluuebunny/crossref_metadata_2025 huggingface dataset:
Segmental Vascular Resistance after Mild Controlled Cortical Impact Injury in the Rat
Authors: Golding Elke M. , Robertson Claudia S. , Fitch Jane C. K. , Goodman J. Clay , Bryan Robert M.
Published: December 2015

In an effort to localize the site at which increased resistance occurs after brain trauma, pial arteriole diameter and pressure were assessed after mild controlled cortical impact (CCI) injury in rats using an open cranial window technique. The authors tested the hypothesis that an increase in resistance accompanied by vasoconstriction occurs at the level of the pial arterioles within the injured cortex of the brain. At 1 hour after mild CCI injury, ipsilateral cerebral blood flow was significantly reduced by 42% compared with sham injury (n = 4; P < 0.05). Pial arteriole diameter and pressure remained unchanged. Resistance in the larger arteries (proximal resistance), however, was significantly greater after CCI injury (1.87 ± 0.26 mm Hg/[mL · 100 g · min]) compared with sham injury (0.91 ± 0.21 mm Hg/[mL · 100 g ·min]; P < 0.0001). Resistance in small vessels, arterioles, and venules (distal resistance) was also significantly greater after CCI injury (1.13 ± 0.05 mm Hg/[mL · 100 g · min]) compared with sham injury (0.74 ± 0.13 mm Hg/[mL · 100 g · min]; P = 0.0001). The authors conclude that, at 1 hour after mild CCI injury, changes in vascular resistance comprise a 53% increase in the resistance distal to the area of injury and, surprisingly, a 105% increase in resistance in the arteries proximal to the injury site.
Protein Histidine Phosphatase: A Novel Enzyme with Potency for Neuronal Signaling
Authors: Klumpp Susanne , Hermesmeier Jan , Selke Dagmar , Baumeister Ralf , Kellner Roland , Krieglstein Josef
Published: December 2015

The importance of reversible phosphorylation for neuronal signaling and cell survival is well recognized. Knowledge in vertebrates, however, is so far limited to O-phosphates from serine, threonine, and tyrosine. The authors describe an enzyme acting on N-phosphates. It is the first protein histidine phosphatase identified in vertebrates. This histidine phosphatase is ubiquitously expressed in mammalian tissues including brain. Characterization and sequencing showed a yet unknown protein with no similarity to other phosphatases. In Caenorhabditis elegans, the homolog of this histidine phosphatase was exclusively expressed in neurons, suggesting a distinct role of reversible histidine phosphorylation in neuronal functions.
Brain Uptake of the Acid Metabolites of F-18—Labeled WAY 100635 Analogs
Authors: Carson Richard E. , Wu Yanjun , Lang Lixin , Ma Ying , Der Margaret G. , Herscovitch Peter , Eckelman William C.
Published: December 2015

The 5-HT1A ligands [F]FPWAY and [18F]FCWAY are metabolized in vivo to [18F]fluorobenzoic acid (FB) and [18F]fluorocyclohexanecarboxylic acid (FC), respectively. To quantify the penetration of these acids into the brain, dynamic positron emission tomography studies were performed in rhesus monkeys with [18F]FB and [18F]FC. High-performance liquid chromatography analysis of arterial blood samples showed no metabolites for [18F]FB, whereas [18F]FC was rapidly metabolized to [18F]fluoride. A model with one tissue compartment and vascular radioactivity was used to analyze gray matter time-activity curves. For [18F]FC, an additional term was added to account for [18F]fluoride skull spillover into the brain; this term accounted for 70% to 90% of the measured radioactivity concentration at 90 minutes. For [18F]FB, mean gray matter parameters were as follows: K1, 10 ± 3 μL · min−1 · mL−1; distribution volume V, 0.052 ± 0.006 (mL/mL). For [18F]FC, the values were as follows: K1, 15 ± 4 μL · min−1 · mL−1; V, 0.29 ± 0.06 mL/mL. The V values were consistent with a physiologic model that included brain-to-blood pH difference and the plasma free fraction of the acid. Simulations based on [18F]FCWAY human data showed that [18F]FC uptake produces significant biases in V estimates in regions with low specific binding. These results can be used to correct the tissue [18F]FCWAY time-activity data for brain uptake of [18F]FC using the measured [18F]FC input function.
Direct Comparison of Local Cerebral Blood Flow Rates Measured by MRI Arterial Spin-Tagging and Quantitative Autoradiography in a Rat Model of Experimental Cerebral Ischemia
Authors: Ewing James R. , Wei Ling , Knight Robert A. , Pawa Swati , Nagaraja Tavarekere N. , Brusca Thomas , Divine George W. , Fenstermacher Joseph D.
Published: December 2015

The present study determined cerebral blood flow (CBF) in the rat using two different magnetic resonance imaging (MRI) arterial spin-tagging (AST) methods and 14C-iodoantipyrine (IAP)-quantitative autoradiography (QAR), a standard but terminal technique used for imaging and quantitating CBF, and compared the resulting data sets to assess the precision and accuracy of the different techniques. Two hours after cerebral ischemia was produced in eight rats via permanent occlusion of one middle cerebral artery (MCA) with an intraluminal suture, MRI-CBF was measured over a 2.0-mm coronal slice using single-coil AST, and tissue magnetization was assessed by either a spin-echo (SE) or a variable tip-angle gradient-echo (VTA-GE) readout. Subsequently (∼2.5 hours after MCA occlusion), CBF was assayed by QAR with the blood flow indicator 14C-IAP, which produced coronal images of local flow rates every 0.4 mm along the rostral—caudal axis. The IAP-QAR images that spanned the 2-mm MRI slice were selected, and regional flow rates (i.e., local CBF [lCBF]) were measured and averaged across this set of images by both the traditional approach, which involved reader interaction and avoidance of sectioning artifacts, and a whole film-scanning technique, which approximated total radioactivity in the entire MRI slice with minimal user bias. After alignment and coregistration, the concordance of the CBF rates generated by the two QAR approaches and the two AST methods was examined for nine regions of interest in each hemisphere. The QAR-lCBF rates were higher with the traditional method of assaying tissue radioactivity than with the MRI-analog approach; although the two sets of rates were highly correlated, the scatter was broad. The flow rates obtained with the whole film-scanning technique were chosen for subsequent comparisons to MRI-CBF results because of the similarity in tissue “sampling” among these three methods. As predicted by previous modeling, “true” flow rates, assumed to be given by QAR-lCBF, tended to be slightly lower than those measured by SE and were appreciably lower than those assessed by VTA-GE. When both the ischemic and contralateral hemispheres were considered together, SE-CBF and VTA-GE-CBF were both highly correlated with QAR-lCBF ( P < 0.001). If evaluated by flow range, however, SE-CBF estimates were more accurate in high-flow (contralateral) areas (CBF > 80 mL · 100 g−1 · min−1), whereas VTA-GE-CBF values were more accurate in low-flow (ipsilateral) areas (CBF ≤ 60 mL · 100 g−1 · min−1). Accordingly, the concurrent usage of both AST-MRI methods or the VTA-GE technique alone would be preferred for human studies of stroke.
Normalization of Endothelial and Inducible Nitric Oxide Synthase Expression in Brain Microvessels of Spontaneously Hypertensive Rats by Angiotensin II AT1 Receptor Inhibition
Authors: Yamakawa Haruki , Jezova Miroslava , Ando Hiromichi , Saavedra Juan M.
Published: December 2015

Inhibition of angiotensin II AT1 receptors protects against stroke, reducing the cerebral blood flow decrease in the periphery of the ischemic lesion. To clarify the mechanism, spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were pretreated with the AT1 receptor antagonist candesartan (0.3 mg · kg−1 · d−1) for 28 days, a treatment identical to that which protected SHR from brain ischemia, and the authors studied middle cerebral artery (MCA) and common carotid morphology, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), and protein expression in cerebral microvessels, principal arteries of the Willis polygon, and common carotid artery. The MCA and common carotid artery of SHR exhibited inward eutrophic remodeling, with decreased lumen diameter and increased media thickness when compared with WKY rats. In addition, there was decreased eNOS and increased iNOS protein and mRNA in common carotid artery, circle of Willis, and brain microvessels of SHR when compared with WKY rats. Both remodeling and alterations in eNOS and iNOS expression in SHR were completely reversed by long-term AT1 receptor inhibition. The hemodynamic, morphologic, and biochemical alterations in hypertension associated with increased vulnerability to brain ischemia are fully reversed by AT1 receptor blockade, indicating that AT1 receptor activation is crucial for the maintenance of the pathologic alterations in cerebrovascular circulation during hypertension, and that their blockade may be of therapeutic advantage.
Ionotropic Glutamate Receptors in Cerebral Microvascular Endothelium are Functionally Linked to Heme Oxygenase
Authors: Parfenova Helena , Fedinec Alex , Leffler Charles W.
Published: December 2015

Vasodilator effects of glutamate in the cerebral circulation are, in part, mediated by carbon monoxide (CO), which is formed from heme via the heme oxygenase (HO) pathway. The hypothesis addressed was that glutamate receptors (GluRs) in cerebral microvascular endothelium are functionally linked to HO. Using a radioligand binding and immunoblotting, GluRs were characterized in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. High-affinity (80 nmol/L) reversible binding of [H]Glutamate ([3H]Glu) was detected in CMVEC membranes. The N-methyl-D-aspartate (NMDA) receptor ligands—NMDA, quinolinic acid, (±)1-aminocyclopentane- cis-1,3-dicarboxylic acid ( cis-ACPD), AP5, 4C3HPG, and CPP—and the (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor ligands—AMPA, kainic acid, quisqualic acid, DNQX, and CNQX—displaced 20% to 30% of bound [3H]Glu in CMVEC membranes. Metabotropic GluRs antagonists (4CPG, PHCC, and CPPG) did not displace bound [3H]Glu. L-Aspartate, an agonist of GluRs and glutamate transporters, displaced 80% or more of bound [3H]Glu. Ionotropic (NR1 and GluR1) and metabotropic (mGluR1α) GluRs were detected in CMVEC by immunoblotting. Glutamate, aspartate, cis-ACPD, AMPA, ( RS)-2-amino-(3-hydroxy-5 -tert-butylisoxazol-4-yl)propanoic acid (ATPA), and kainate (10−5 mol/L) increased HO-directed CO formation by isolated cerebral microvessels and by cultured CMVEC. These data in newborn pigs suggest that CMVEC express ionotropic GluRs that are functionally linked to HO. GluR-mediated increases in CO formation by vascular endothelium may result in increase in cerebral blood flow.
Blood Genomic Expression Profile for Neuronal Injury
Authors: Tang Yang , Nee Alex C. , Lu Aigang , Ran Ruiqiong , Sharp Frank R.
Published: December 2015

This study determined whether stroke and other types of insults produced a gene expression profile in blood that correlated with the presence of neuronal injury. Adult rats were subjected to ischemic stroke, intracerebral hemorrhage, status epilepticus, and insulin-induced hypoglycemia and compared with untouched, sham surgery, and hypoxia animals that had no brain injury. One day later, microarray analyses showed that 117 genes were upregulated and 80 genes were downregulated in mononuclear blood cells of the “injury” (n = 12) compared with the “no injury” (n = 9) animals. A second experiment examined the whole blood genomic response of adult rats after global ischemia and kainate seizures. Animals with no brain injury were compared with those with brain injury documented by TUNEL and PANT staining. One day later, microarray analyses showed that 37 genes were upregulated and 67 genes were downregulated in whole blood of the injury (n = 4) animals compared with the no-injury (n = 4) animals. Quantitative reverse transcription–polymerase chain reaction confirmed that the vesicular monoamine transporter-2 increased 2.3- and 1.6-fold in animals with severe and mild brain injury, respectively, compared with no-injury animals. Vascular tyrosine phosphatase-1 increased 2.0-fold after severe injury compared with no injury. The data support the hypothesis that there is a peripheral blood genomic response to neuronal injury, and that this blood response is associated with a specific blood mRNA gene expression profile that can be used as a marker of the neuronal damage.
Role of P2X7 Receptors in Ischemic and Excitotoxic Brain Injury In Vivo
Authors: Le Feuvre Rosalind A. , Brough David , Touzani Omar , Rothwell Nancy J.
Published: December 2015

Purinergic P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1β (IL-1β), a key mediator in neurodegeneration. The authors tested the hypothesis that ATP, acting at P2X7 receptors, contributes to experimentally induced neuronal death in rodents in vivo. Deletion of P2X7 receptors (P2X7 knockout mice) did not affect cell death induced by temporary cerebral ischemia, which was reduced by treatment with IL-1 receptor antagonist (IL-1RA). Treatment of mice with P2X antagonists did not affect ischemic or excitotoxic cell death, suggesting that P2X7 receptors are not primary mediators of experimentally induced neuronal death.
Temporal Profile of Stem Cell Division, Migration, and Differentiation from Subventricular Zone to Olfactory Bulb after Transient Forebrain Ischemia in Gerbils
Authors: Iwai Masanori , Sato Keiko , Kamada Hiroshi , Omori Nobuhiko , Nagano Isao , Shoji Mikio , Abe Koji
Published: December 2015

The stage of neurogenesis can be divided into three steps: proliferation, migration, and differentiation. To elucidate their detailed relations after ischemia, the three steps were comprehensively evaluated, in the subventricular zone (SVZ) through the rostral migratory stream (RMS) to the olfactory bulb (OB), in adult gerbil brain after 5 minutes of transient forebrain ischemia. Bromodeoxyuridine (BrdU), highly polysialylated neural cell adhesion molecule (PSA-NCAM), neuronal nuclear antigen (NeuN), and glial fibrillary acidic protein (GFAP) were used as markers for proliferation, migration, and differentiation, respectively. The number of BrdU-labeled cells that coexpressed PSA-NCAM and the size of PSA-NCAM–positive cell colony increased in the SVZ with a peak at 10 d after transient ischemia. In the RMS, the number of BrdU-labeled cells that coexpressed PSA-NCAM increased, with a delayed peak at 30 d, when the size of RMS itself became larger and the number of surrounding GFAP-positive cells increased. In the OB, BrdU + NeuN double positive cells were detected at 30 and 60 d. NeuN staining and terminal deoxynucleotidyl dUTP nick-end labeling staining showed no neuronal cell loss around the SVZ, and in the RMS and the OB after transient ischemia. These findings indicate that transient forebrain ischemia enhances neural stem cell proliferation in the SVZ without evident neuronal cell loss, and has potential neuronal precursor migration with activation of GFAP-positive cells through the RMS to the OB.
Apaf-1, Bcl-xL, Cytochrome c, and Caspase-9 Form the Critical Elements for Cerebral Vascular Protection by Erythropoietin
Authors: Chong Zhao Zhong , Kang Jing-Qiong , Maiese Kenneth
Published: December 2015

Erythropoietin (EPO) plays a prominent role in the regulation of the hematopoietic system, but the potential function of this trophic factor as a cytoprotectant in the cerebral vascular system is not known. The authors examined the ability of EPO to modulate a series of death-related cellular pathways during free radical–induced injury in cerebral microvascular endothelial cells (ECs). Endothelial cell injury was evaluated by trypan blue, DNA fragmentation, membrane phosphatidylserine exposure, apoptotic protease–activating factor-1 (Apaf-1), and Bcl-xL expression, mitochondrial membrane potential, cytochrome c release, and cysteine protease activity. They show that constitutive EPO is present in ECs but is insufficient to prevent cellular injury. Signaling through the EPO receptor, however, remains biologically responsive to exogenous EPO administration to offer significant protection against nitric oxide–induced injury. Exogenous EPO maintains both genomic DNA integrity and cellular membrane asymmetry through parallel pathways that prevent the induction of Apaf-1 and preserve mitochondrial membrane potential in conjunction with enhanced Bcl-xL expression. Consistent with the modulation of Apaf-1 and the release of cytochrome c, EPO also inhibits the activation of caspase-9 and caspase-3–like activities. Identification of novel cytoprotective pathways used by EPO may serve as therapeutic targets for cerebral vascular disease.
Rat Organic Anion Transporter 3 (rOAT3) is Responsible for Brain-to-Blood Efflux of Homovanillic Acid at the Abluminal Membrane of Brain Capillary Endothelial Cells
Authors: Mori Shinobu , Takanaga Hitomi , Ohtsuki Sumio , Deguchi Tsuneo , Kang Young-Sook , Hosoya Ken-ichi , Terasaki Tetsuya
Published: December 2015

The mechanism that removes homovanillic acid (HVA), an end metabolite of dopamine, from the brain is still poorly understood. The purpose of this study is to identify and characterize the brain-to-blood HVA efflux transporter at the rat blood–brain barrier (BBB). Using the Brain Efflux Index method, the apparent in vivo efflux rate constant of [3H]HVA from the brain, keff, was determined to be 1.69 × 10–2 minute–1. This elimination was significantly inhibited by para-aminohippuric acid (PAH), benzylpenicillin, indoxyl sulfate, and cimetidine, suggesting the involvement of rat organic anion transporter 3 (rOAT3). rOAT3-expressing oocytes exhibited [3H]HVA uptake (Km = 274 μmol/L), which was inhibited by several organic anions, such as PAH, indoxyl sulfate, octanoic acid, and metabolites of monoamine neurotransmitters. Neurotransmitters themselves did not affect the uptake. Furthermore, immunohistochemical analysis suggested that rOAT3 is localized at the abluminal membrane of brain capillary endothelial cells. These results provide the first evidence that rOAT3 is expressed at the abluminal membrane of the rat BBB and is involved in the brain-to-blood transport of HVA. This HVA efflux transport system is likely to play an important role in controlling the level of HVA in the CNS.
Absolute Cerebral Blood Volume and Blood Flow Measurements Based on Synchrotron Radiation Quantitative Computed Tomography
Authors: Adam Jean-François , Elleaume Hélène , Duc Géraldine Le , Corde Stéphanie , Charvet Anne-Marie , Troprès Irène , Bas Jean-François Le , Estève François
Published: December 2015

Synchrotron radiation computed tomography opens new fields by using monochromatic x-ray beams. This technique allows one to measure in vivo absolute contrast-agent concentrations with high accuracy and precision, and absolute cerebral blood volume or flow can be derived from these measurements using tracer kinetic methods. The authors injected an intravenous bolus of an iodinated contrast agent in healthy rats, and acquired computed tomography images to follow the temporal evolution of the contrast material in the blood circulation. The first image acquired before iodine infusion was subtracted from the others to obtain computed tomography slices expressed in absolute iodine concentrations. Cerebral blood volume and cerebral blood flow maps were obtained after correction for partial volume effects. Mean cerebral blood volume and flow values (n = 7) were 2.1 ± 0.38 mL/100 g and 129 ± 18 mL · 100 g–1 · min–1 in the parietal cortex; and 1.92 ± 0.32 mL/100 g and 125 ± 17 mL · 100 g–1 · min–1 in the caudate putamen, respectively. Synchrotron radiation computed tomography has the potential to assess these two brain-perfusion parameters.
Delayed Cerebrovascular Protective Effect of Lipopolysaccharide in Parallel to Brain Ischemic Tolerance
Authors: Bastide Michèle , Gelé Patrick , Pétrault Olivier , Pu Qian , Caliez Audrey , Robin Emmanuel , Deplanque Dominique , Duriez Patrick , Bordet Régis
Published: December 2015

Cerebrovascular abnormalities, in endothelium and smooth muscle compartments, occur in the course of cerebral ischemia–reperfusion as evidenced by the impairment of endothelium-dependent relaxation and decrease in potassium inward rectifier density in occluded middle cerebral arteries (MCAs). The authors investigated whether a delayed vascular protection occurred in a model of brain ischemic tolerance. A low dose of lipopolysaccharide (0.3 mg/kg) administered 72 h before MCA occlusion induced a significant decrease in infarct volume. In parallel to this delayed neuroprotective effect, lipopolysaccharide prevented the ischemia–reperfusion–induced impairment of endothelium relaxation. In addition, lipopolysaccharide prevented the postischemic alteration of potassium inward rectifier–dependent smooth muscle relaxation as well as the decrease in potassium inward rectifier density measured by patch-clamp in dissociated vascular smooth muscle cells originated from the occluded MCA. These results suggest that during brain ischemic tolerance, lipopolysaccharide is able to induce both a delayed neuroprotective and vasculoprotective effect.
Reversible Loss of N-Acetyl-Aspartate in Rats Subjected to Long-Term Focal Cerebral Ischemia
Authors: Demougeot Céline , Bertrand Nathalie , Prigent-Tessier Anne , Garnier Philippe , Mossiat Claude , Giroud Maurice , Marie Christine , Beley Alain
Published: December 2015

To evaluate the true meaning of N-acetyl-aspartate (NAA) measurements in ischemic stroke, the authors followed the temporal changes in brain NAA content in rats subjected to permanent focal ischemia. Ischemia was induced by photothrombotic cortical occlusion. At 1, 3, 8, and 30 d after onset of ischemia, NAA was measured in the infarct by high-performance liquid chromatography coupled to ultraviolet detection and histologic damage was examined. Cerebral content of NAA was markedly reduced in the lesioned tissue, reaching −90% after 3 d, a time at which viable neurons were no longer detected. N-Acetyl-aspartate concentrations after 8 and 30 d were higher than that observed after 3 d. This metabolic change coincided with an important microglial and astroglial activation. The results of this study raise questions regarding the use of NAA as a specific neuronal marker in chronic stage of stroke.
Bradykinin Antagonists Reduce Leukocyte–Endothelium Interactions after Global Cerebral Ischemia
Authors: Lehmberg Jens , Beck Jürgen , Baethmann Alexander , Uhl Eberhard
Published: December 2015

The aim of the present study was to evaluate the influence of bradykinin on microcirculatory changes and outcome after global cerebral ischemia (15 minute) in Mongolian gerbils. The cerebral microcirculation was investigated by fluorescent intravital microscopy. Survival and functional outcome was evaluated up to 4 d after ischemia. Animals were treated with the selective B1 and B2 receptor antagonists B 9858 and CP 0597, respectively, and the nonselective B1/B2 receptor antagonist B 9430. Leukocyte activation was significantly reduced by all antagonists as indicated by a significant decrease in the number of rolling (33 ± 20, 6 ± 8, 9 ± 10, and 13 ± 10) and adherent leukocytes (9 ± 7, 3 ± 4, 1 ± 1, and 2 ± 3 · 100 μm–1 · min–1 in controls and in animals treated with B1, B2, and B1/B2 antagonist, respectively). Arteriolar diameters were significantly reduced during reperfusion (35 ± 11 before and 27 ± 8 μm 40 minutes after ischemia) in animals treated with the B2 antagonist. The postischemic hypoperfusion, however, was not affected. Mortality was significantly higher in animals treated with the B1 and the B1/B2 antagonist. The authors concluded that bradykinin is involved in postischemic disturbances of cerebral microcirculation. The therapeutic effect of specific bradykinin receptor antagonists on functional outcome, however, remains unclear.
Oligodendrocytes and Ischemic Brain Injury
Authors: Dewar Deborah , Underhill Suzanne M. , Goldberg Mark P.
Published: December 2015

Oligodendrocytes, myelin-forming glial cells of the central nervous system, are vulnerable to damage in a variety of neurologic diseases. Much is known of primary myelin injury, which occurs in settings of genetic dysmyelination or demyelinating disease. There is growing awareness that oligodendrocytes are also targets of injury in acute ischemia. Recognition of oligodendrocyte damage in animal models of ischemia requires attention to their distinct histologic features or use of specific immunocytochemical markers. Like neurons, oligodendrocytes are highly sensitive to injury by oxidative stress, excitatory amino acids, trophic factor deprivation, and activation of apoptotic pathways. Understanding mechanisms of oligodendrocyte death may suggest new therapeutic strategies to preserve or restore white matter function and structure after ischemic insults.
Regional Cerebral Blood Flow and BOLD Responses in Conscious and Anesthetized Rats under Basal and Hypercapnic Conditions: Implications for Functional MRI Studies
Authors: Sicard Kenneth , Shen Qiang , Brevard Mathew E. , Sullivan Ross , Ferris Craig F. , King Jean A. , Duong Timothy Q.
Published: December 2015

Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level–dependent [BOLD]) were measured, using the continuous arterial-spin-labeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia ( P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 ± 0.25 and 1.27 ± 0.29 mL · g–1 · min–1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state ( P < 0.01). Hypercapnia decreased pH, and increased Pco2 and Po2. During 5% CO2 challenge, under awake and anesthetized conditions, respectively, CBF increased 51 ± 11% and 25 ± 4%, and BOLD increased 7.3 ± 0.7% and 5.4 ± 0.4%. During 10% CO2 challenge, CBF increased 158 ± 28% and 47 ± 11%, and BOLD increased 12.5 ± 0.9% and 7.2 ± 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.
Macrophages and Microglia in Central Nervous System Injury: Are They Helpful or Harmful?
Authors: Schwartz Michal
Published: December 2015

Inflammation has been widely perceived as participating in the etiology of acute and chronic neurodegenerative conditions. Accordingly, in the context of traumatic injuries or chronic neurodegenerative diseases in the central nervous system (CNS), activated microglia have been viewed as detrimental and attempts have been made to treat both conditions by antiinflammatory therapy. Recent studies have suggested that microglia act as stand-by cells in the service of both the immune and the nervous systems. In the healthy CNS these cells are quiescent, but in the event of injury to axons or cell bodies they exercise their neural function by buffering harmful self-compounds and clearing debris from the damaged site, and their immune function by providing immune-related requirements for recovery. Proper regulation of the inflammatory (autoimmune) response to injury will arrest degeneration and promote regrowth, whereas inappropriate regulation will lead to ongoing degeneration. Regulation is achieved by the operation of a T cell–mediated response directed to abundant self-antigens residing in the damaged site. Since this immune-dependent mechanism was found to protect against glutamate toxicity (a major factor in neurodegenerative disorders), boosting of this response might constitute the basis for development of a therapeutic vaccination against neurodegenerative diseases, all of which exhibit similar pathways and patterns of progression.
Management of Pediatric Perforated Appendicitis
Authors: Bonadio William , Rebillot Katie , Ukwuoma Onyinyechi , Saracino Christine , Iskhakov Arthur
Published: December 2015

Background:

There is controversy regarding whether children with perforated appendicitis should receive early appendectomy (EA) versus medical management (MM) with antibiotics and delayed interval appendectomy. The objective of this study was to compare outcomes of children with perforated appendicitis who receive EA versus MM.

Methods:

Case review of consecutive children <18 years of age with perforated appendicitis who received either EA or MM during an 8-year period. Criteria for hospital discharge included patient being afebrile for at least 24 hours, pain-free and able to tolerate oral intake.

Results:

Of 203 patients diagnosed with perforated appendicitis, 122 received EA and 81 received MM. All received parenteral antibiotic therapy initiated in the emergency department and continued during hospitalization. There were no significant differences between groups in mean patient age, mean complete blood count total white blood cells count, gender distribution, rates of emergency department fever or rates of intra-abdominal infection (abscess or phlegmon) identified on admission. Compared with patients receiving MM, those receiving EA experienced significantly fewer (1) days of hospitalization, parenteral antibiotic therapy and in-hospital fever; (2) radiographic studies, percutaneous drainage procedures and placement of central venous catheters performed; (3) post admission intra-abdominal complications and (4) unscheduled repeat hospitalizations after hospital discharge. Only 1 EA-managed patient developed a postoperative wound infection.

Conclusions:

Children with perforated appendicitis who receive EA experience significantly less morbidity and complications versus those receiving MM. The theoretical concern for enhanced morbidity associated with EA management of perforated appendicitis is not supported by our analysis.
Successful Treatment of Extensive Squamous Cell Carcinoma of the Conjunctiva and Upper Eyelid Skin With Topical Therapy Alone
Authors: Huang Grace , Mirani Neena , Connally Adrian , Langer Paul D.
Published: December 2015

This study reports a case of extensive periocular squamous cell carcinoma of the conjunctiva, extending into the superior fornix, over the upper eyelid margin, and involving the superficial layers of the eyelid skin up to the eyebrow, that was successfully treated solely with topical therapy.
Fecal Impaction in the Emergency Department
Authors: Corban Caroline , Sommers Thomas , Sengupta Neil , Jones Mike , Cheng Vivian , Friedlander Elizabeth , Bollom Andrea , Lembo Anthony
Published: December 2015

Goals:

The aim of this study was to analyze the incidence and associated charges of fecal impaction for trends in hospital and patient demographics in emergency departments (ED) across the United States.

Background:

In 2010, an ICD-9-CM code (560.32) for fecal impaction was introduced, allowing for assessment of fecal impaction incidence.

Study:

Data were obtained from the National Emergency Department Sample records in which fecal impaction (ICD-9-CM code 560.32) was first listed as a diagnosis in 2011.

Results:

In 2011, there were 42,481 [95% confidence interval (CI), 39,908-45,054] fecal impaction ED visits, with an overall rate of 32 fecal impaction visits per 100,000 ED visits. Adjusted for inflation in 2014 dollars, the associated mean charge of a fecal impaction ED visit was $3060.47 (95% CI, $2943.02-$3177.92), with an aggregate national charge in the US of $130,010,772 (95% CI, $120,688,659-$139,332,885). All charges were adjusted for inflation and reported in 2014 dollars. Late elders (85+ y) had the highest rate of fecal impaction ED visits, followed by early elders (65 to 84 y). Medicare was the primary payer for the greatest number of fecal impaction ED visits accounting for nearly two thirds of visit payments.

Conclusion:

This study reports previously unexplored statistics on the number, frequency, and associated charges of ED visits with a primary diagnosis of fecal impaction, a condition found most commonly among elders.
Subglacial Lake Whillans microbial biogeochemistry: a synthesis of current knowledge
Authors: Mikucki J. A. , Lee P. A. , Ghosh D. , Purcell A. M. , Mitchell A. C. , Mankoff K. D. , Fisher A. T. , Tulaczyk S. , Carter S. , Siegfried M. R. , Fricker H. A. , Hodson T. , Coenen J. , Powell R. , Scherer R. , Vick-Majors T. , Achberger A. A. , Christner B. C. , Tranter M. ,   the WISSARD Science Team
Published: December 2015

Liquid water occurs below glaciers and ice sheets globally, enabling the existence of an array of aquatic microbial ecosystems. In Antarctica, large subglacial lakes are present beneath hundreds to thousands of metres of ice, and scientific interest in exploring these environments has escalated over the past decade. After years of planning, the first team of scientists and engineers cleanly accessed and retrieved pristine samples from a West Antarctic subglacial lake ecosystem in January 2013. This paper reviews the findings to date on Subglacial Lake Whillans and presents new supporting data on the carbon and energy metabolism of resident microbes. The analysis of water and sediments from the lake revealed a diverse microbial community composed of bacteria and archaea that are close relatives of species known to use reduced N, S or Fe and CH4as energy sources. The water chemistry of Subglacial Lake Whillans was dominated by weathering products from silicate minerals with a minor influence from seawater. Contributions to water chemistry from microbial sulfide oxidation and carbonation reactions were supported by genomic data. Collectively, these results provide unequivocal evidence that subglacial environments in this region of West Antarctica host active microbial ecosystems that participate in subglacial biogeochemical cycling.
Advances in modelling subglacial lakes and their interaction with the Antarctic ice sheet
Authors: Pattyn Frank , Carter Sasha P. , Thoma Malte
Published: December 2015

Subglacial lakes have long been considered hydraulically isolated water bodies underneath ice sheets. This view changed radically with the advent of repeat-pass satellite altimetry and the discovery of multiple lake discharges and water infill, associated with water transfer over distances of more than 200 km. The presence of subglacial lakes also influences ice dynamics, leading to glacier acceleration. Furthermore, subglacial melting under the Antarctic ice sheet is more widespread than previously thought, and subglacial melt rates may explain the availability for water storage in subglacial lakes and water transport. Modelling of subglacial water discharge in subglacial lakes essentially follows hydraulics of subglacial channels on a hard bed, where ice sheet surface slope is a major control on triggering subglacial lake discharge. Recent evidence also points to the development of channels in deformable sediment in West Antarctica, with significant water exchanges between till and ice. Most active lakes drain over short time scales and respond rapidly to upstream variations. Several Antarctic subglacial lakes exhibit complex interactions with the ice sheet due to water circulation. Subglacial lakes can therefore—from a modelling point of view—be seen as confined small oceans underneath an imbedded ice shelf.
Geology and environments of subglacial Lake Vostok
Authors: Leitchenkov German L. , Antonov Anton V. , Luneov Pavel I. , Lipenkov Vladimir Ya.
Published: December 2015

The reconstruction of the geological (tectonic) structure and environments of subglacial Lake Vostok is based on geophysical surveys and the study of mineral particles found in cores of accreted ice and frozen lake water (sampled after the lake was unsealed). Seismic reflection and refraction investigations conducted in the southern part of Lake Vostok show very thin (200–300 m) sedimentary cover overlying a crystalline basement. Most of this thin veneer is thought to have been deposited during temperate-glacial conditions in Oligocene to Middle Miocene time (
ca
34–14 Ma). The composition of the lake-bottom sediments can be deduced from mineral inclusions found in cores of accreted ice. Inclusions are represented by soft aggregates consisting mainly of clay–mica minerals and micrometre-sized quartz grains. Some of these inclusions contain subangular to semi-rounded rock clasts (siltstones and sandstones) ranging from 0.3 to 8 mm in size. In total, 31 zircon grains have been identified in two rock clasts and dated using SHRIMP-II. The ages of the studied zircons range from 0.6 to 2.0 Ga with two distinct clusters between 0.8 and 1.15 Ga and between 1.6 and 1.8 Ga. Rock clasts obviously came from the western lake shore, which is thus composed of terrigenous strata with an age of not older than 600 Ma. The sedimentary nature of the western lake shore is also confirmed by seismic refraction data showing seismic velocities there of 5.4–5.5 km s
−1
at the bedrock surface. After Lake Vostok was unsealed, its water (frozen and sampled next season) was also studied with scanning electron microscopy and X-ray microprobe analysis. This study showed the existence of calcium carbonate and silica microparticles (10–20 μm across) in frozen water.
Recent advances in understanding Antarctic subglacial lakes and hydrology
Authors: Siegert Martin J. , Ross Neil , Le Brocq Anne M.
Published: December 2015

It is now well documented that over 400 subglacial lakes exist across the bed of the Antarctic Ice Sheet. They comprise a variety of sizes and volumes (from the approx. 250 km long Lake Vostok to bodies of water less than 1 km in length), relate to a number of discrete topographic settings (from those contained within valleys to lakes that reside in broad flat terrain) and exhibit a range of dynamic behaviours (from ‘active’ lakes that periodically outburst some or all of their water to those isolated hydrologically for millions of years). Here we critique recent advances in our understanding of subglacial lakes, in particular since the last inventory in 2012. We show that within 3 years our knowledge of the hydrological processes at the ice-sheet base has advanced considerably. We describe evidence for further ‘active’ subglacial lakes, based on satellite observation of ice-surface changes, and discuss why detection of many ‘active’ lakes is not resolved in traditional radio-echo sounding methods. We go on to review evidence for large-scale subglacial water flow in Antarctica, including the discovery of ancient channels developed by former hydrological processes. We end by predicting areas where future discoveries may be possible, including the detection, measurement and significance of groundwater (i.e. water held beneath the ice-bed interface).
Radiating despite a lack of character: closely related, morphologically similar, co-occurring honeyeaters have diverged ecologically
Authors: Miller Eliot T. , Wagner Sarah K. , Harmon Luke J. , Ricklefs Robert E.
Published: December 2015

The 75 species of Australian honeyeaters (Meliphagidae) are morphologically and ecologically diverse, with species feeding on nectar, insects, fruit, and other resources. We investigated ecomorphology and community structure of honeyeaters across Australia. First, we asked to what degree morphology and ecology (foraging behavior) are concordant. Second, we estimated rates of trait evolution. Third, we compared phylogenetic and trait community structure across the broad environmental gradients of continental Australia. We found that morphology explained 37% of the variance in ecology (and 62% vice versa), and that recovered multivariate ecomorphological relationships incorporated well-known bivariate relationships. Clades of large-bodied species exhibited elevated rates of morphological trait evolution, while members ofMelithreptusshowed slightly faster rates of ecological trait evolution. Finally, ecological trait diversity did not decline in parallel with phylogenetic diversity along a gradient of decreasing precipitation. We employ a new method (trait fields) and extend another (phylogenetic fields) to show that while species from phylogenetically clustered assemblages co-occur with morphologically similar species, these species are as varied in foraging behavior as those from more diverse assemblages. Thus, although closely related, these arid-adapted species have diverged in ecological space to a similar degree as their mesic counterparts, perhaps mediated by competition.
RBS-sponsored Sprint as Springboard for women undergraduates
'
success
Authors: Little Bob
Published: December 2015

Purpose

– The purpose of this paper is to set out the results of research which showed the gender pay gap among graduates and outline some of the steps being taken to combat this. In particular, it outlines the Sprint programme, developed for women undergraduates. This programme aims to add value to the overall student experience at university, improve employability and help to ensure that each undergraduate – regardless of her subject, department or career aspirations – can develop to her fullest potential.

Design/methodology/approach

– This paper comprises results of research carried out by Oxford University’s Careers Service. It also contains the results of interviews with the developers, deliverers, sponsors and users of the Sprint programme – a programme which was developed as a response to these research findings.

Findings

– The Sprint programme helps women focus on their studies at university, achieving results such as improved visibility and effectiveness in tutorials, better time management, less study stress, a boost in confidence and self-esteem. They also use Sprint to sharpen their career goals, raise their aspirations, explore possibilities and to take advantage of the work shadowing, internships and mentoring often offered by corporate sponsors. Participants in the Sprint programme also tend to find it also helps them to achieve results in their personal lives – such as sorting out difficult relationships, improving fitness and gaining a better study/life balance.

Research limitations/implications

– It is possible to bridge the gender pay gap as well as benefit women in other ways via learning and development activities, such as those promoted via the Sprint programme.

Practical implications

– With help from programmes such as Sprint, women can achieve improved work visibility and effectiveness, better time management, reduced stress, increased confidence and self-esteem. This helps them achieve their career goals, raise their aspirations and generally develop their careers.

Social implications

– Women can be helped to compete effectively with men in the workplace as well as be successful in their personal lives (in terms of sorting out difficult relationships, improving fitness and gaining a better study/life balance). This offers many benefits for women – and for the well-being of society in general.

Originality/value

– The Sprint programme, along with the approach of The Springboard Consultancy, is unique. Although the Sprint programme is relatively new – having started in 2013 – it is already bearing positive results.
Re-discovering Charles Clinton Spaulding’s “The Administration of Big Business”
Authors: Prieto Leon C. , Phipps Simone T. A.
Published: December 2015

Purpose

– The purpose of this paper is to reveal the contributions made by Charles Clinton Spaulding, a prominent black business leader in the USA in the early 1900s. This paper highlights the management philosophies and practical work of Spaulding, an individual who considerably influenced African-American management thought and practice, and played an important role in Corporate America from the turn of the twentieth century onward.

Design/methodology/approach

– The research was conducted by reviewing and synthesizing a number of writings including published works by Spaulding himself, as well as articles about Spaulding from sources such as history journals, newspapers and other resources.

Findings

– Spaulding’s contributions were significant, from his insight regarding the fundamental necessities for the effective management of a business, to his management style and implementation of practices which reflected his recognition of the importance of transformational leadership, employee development, diversity, corporate social responsibility and a strong positive culture for the successful management of an enterprise. Thus, this paper concludes that the title of “Father of African-American Management” is a fitting tribute to this business pioneer who overcame the odds to become the most successful black business executive in the early twentieth century.

Originality/value

– The contributions made by minorities, including African-Americans, to management thought and practice have not been adequately covered in the literature. This paper begins to fill a noticeable void by drawing from infrequently acquired sources such as Spaulding’s article “The Administration of Big Business” and highlighting his contributions to the African-American community and the business community at large.
When the moral tail wags the entrepreneurial dog: the historic case of Trumpet Records
Authors: Winstead Jack L. , Novicevic Milorad M. , Humphreys John H. , Popoola Ifeoluwa Tobi
Published: December 2015

Purpose

– The purpose of this paper is to explore the congruencies and incongruences between the moral and entrepreneurial accountabilities of Lillian McMurry to provide insights for entrepreneurs and entrepreneurship. Ms McMurry was the entrepreneurial force behind the founding of Trumpet Records, a unique, Mississippi Delta Blues record label in the 1950s.

Design/methodology/approach

– The examination of this historical case study is grounded in the theoretical examination of the tensions between Lillian McMurry’s felt moral and entrepreneurial accountabilities. Using an analytical archival historical method, a narrative explanation of how these tensions influenced the success and, ultimately, the failure of Trumpet Records are developed.

Findings

– The accounting records highlighted a number of issues hampering the commercial profitability of Trumpet Records. Moreover, the archival and documentary sources examined also proved revealing as to conflicts between Ms McMurry’s personal character and mercantile determination as an entrepreneur.

Research limitations/implications

– The approach of using analytically structured historical narrative as a research strategy is but one method of explaining the tensions between the moral and entrepreneurial accountabilities of Lillian McMurry.

Practical implications

– The proponents of virtue ethics suggest that this Aristotelian personal character perspective is more fundamental than traditional, act-oriented consequentialist teleological and deontological ethical decision-making approaches. A perspective of moral accountability exceeding the norm of the obstructionist stance is required to maintain a sound balance between entrepreneurial accountability and moral accountability.

Originality/value

– This paper adopts a mercantile perspective, using the accounting and related business records of Trumpet Records, to examine the leadership characteristics of Lillian McMurry. Practical lessons learned for entrepreneurs facing the moral dilemma of competing accountabilities and advance questions to spur future research in this area are drawn.