bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma radiometabolite correction in dynamic PET studies: Insights on the available modeling approaches
Authors: Tonietto Matteo , Rizzo Gaia , Veronese Mattia , Fujita Masahiro , Zoghbi Sami S , Zanotti-Fregonara Paolo , Bertoldo Alessandra
Published: December 2015

Full kinetic modeling of dynamic PET images requires the measurement of radioligand concentrations in the arterial plasma. The unchanged parent radioligand must, however, be separated from its radiometabolites by chromatographic methods. Thus, only few samples can usually be analyzed and the resulting measurements are often noisy. Therefore, the measurements must be fitted with a mathematical model. This work presents a comprehensive analysis of the different models proposed in the literature to describe the plasma parent fraction (PPf) and of the alternative approaches for radiometabolite correction. Finally, we used a dataset of [11C]PBR28 brain PET data as a case study to guide the reader through the PPf model selection process.
Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats
Authors: Liu Da Zhi , Jickling Glen C , Ander Bradley P , Hull Heather , Zhan Xinhua , Cox Christopher , Shroff Natasha , Dykstra-Aiello Cheryl , Stamova Boryana , Sharp Frank R
Published: December 2015

Because our recent studies have demonstrated that miR-122 decreased in whole blood of patients and in whole blood of rats following ischemic stroke, we tested whether elevating blood miR-122 would improve stroke outcomes in rats. Young adult rats were subjected to a temporary middle cerebral artery occlusion (MCAO) or sham operation. A polyethylene glycol-liposome-based transfection system was used to administer a miR-122 mimic after MCAO. Neurological deficits, brain infarction, brain vessel integrity, adhesion molecule expression and expression of miR-122 target and indirect-target genes were examined in blood at 24 h after MCAO with or without miR-122 treatment. miR-122 decreased in blood after MCAO, whereas miR-122 mimic elevated miR-122 in blood 24 h after MCAO. Intravenous but not intracerebroventricular injection of miR-122 mimic decreased neurological deficits and brain infarction, attenuated ICAM-1 expression, and maintained vessel integrity after MCAO. The miR-122 mimic also down-regulated direct target genes (e.g. Vcam1, Nos2, Pla2g2a) and indirect target genes (e.g. Alox5, Itga2b, Timp3, Il1b, Il2, Mmp8) in blood after MCAO which are predicted to affect cell adhesion, diapedesis, leukocyte extravasation, eicosanoid and atherosclerosis signaling. The data show that elevating miR-122 improves stroke outcomes and we postulate this occurs via downregulating miR-122 target genes in blood leukocytes.
Extracellular ʜ ᴄ ᴏ3̅ is sensed by mouse cerebral arteries: Regulation of tone by receptor protein tyrosine phosphatase γ
Authors: Boedtkjer Ebbe , Hansen Kristoffer B , Boedtkjer Donna MB , Aalkjaer Christian , Boron Walter F
Published: December 2015

We investigate sensing and signaling mechanisms for H+, [Formula: see text] and CO2 in basilar arteries using out-of-equilibrium solutions. Selectively varying pHo, [[Formula: see text]]o, or pCO2, we find: (a) lowering pHo attenuates vasoconstriction and vascular smooth muscle cell (VSMC) Ca2+-responses whereas raising pHo augments vasoconstriction independently of VSMC [Ca2+]i, (b) lowering [[Formula: see text]]o increases arterial agonist-sensitivity of tone development without affecting VSMC [Ca2+]i but c) no evidence that CO2 has direct net vasomotor effects. Receptor protein tyrosine phosphatase (RPTP)γ is transcribed in endothelial cells, and direct vasomotor effects of [Formula: see text] are absent in arteries from RPTPγ-knockout mice. At pHo 7.4, selective changes in [[Formula: see text]]o or pCO2 have little effect on pHi. At pHo 7.1, decreased [[Formula: see text]]o or increased pCO2 causes intracellular acidification, which attenuates vasoconstriction. Under equilibrated conditions, anti-contractile effects of CO2/[Formula: see text] are endothelium-dependent and absent in arteries from RPTPγ-knockout mice. With CO2/[Formula: see text] present, contractile responses to agonist-stimulation are potentiated in arteries from RPTPγ-knockout compared to wild-type mice, and this difference is larger for respiratory than metabolic acidosis. In conclusion, decreased pHo and pHi inhibit vasoconstriction, whereas decreased [[Formula: see text]]o promotes vasoconstriction through RPTPγ-dependent changes in VSMC Ca2+-sensitivity. [Formula: see text] serves dual roles, providing substrate for pHi-regulating membrane transporters and modulating arterial responses to acid–base disturbances.
Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice
Authors: Chandra Saurav B , Mohan Sumathy , Ford Bridget M , Huang Lei , Janardhanan Preethi , Deo Kaiwalya S , Cong Linlin , Muir Eric R , Duong Timothy Q
Published: December 2015

Reduced bioavailability of nitric oxide due to impaired endothelial nitric oxide synthase (eNOS) activity is a leading cause of endothelial dysfunction in diabetes. Enhancing eNOS activity in diabetes is a potential therapeutic target. This study investigated basal cerebral blood flow and cerebrovascular reactivity in wild-type mice, diabetic mice (Ins2Akita+/−), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2Akita+/−) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2Akita+/− and TgeNOS-Ins2Akita+/− were significantly different from wild-type and TgeNOS mice. Blood pressure of TgeNOS mice was lower than wild-type. (ii) Basal cerebral blood flow of the TgeNOS group was significantly higher than cerebral blood flow of the other three groups. (iii) The cerebrovascular reactivity in the Ins2Akita+/− mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2Akita+/− was significantly higher compared with the Ins2Akita+/− and TgeNOS groups. Overexpression of eNOS rescued cerebrovascular dysfunction in diabetic animals, resulting in improved cerebrovascular reactivity. These results underscore the possible role of eNOS in vascular dysfunction in the brain of diabetic mice and support the notion that enhancing eNOS activity in diabetes is a potential therapeutic target.
Efficacy of the PSD95 inhibitor Tat-NR2B9c in mice requires dose translation between species
Authors: Teves Lucy M , Cui Hong , Tymianski Michael
Published: December 2015

Tat-NR2B9c, a clinical-stage stroke neuroprotectant validated in rats and primates, was recently deemed ineffective in mice. To evaluate this discrepancy, we conducted studies in mice subjected to temporary middle cerebral artery occlusion (tMCAO) for either 30 or 60 min according to the established principles for dose-translation between species. Tat-NR2B9c treatment reduced infarct volume by by 24.5% ( p = 0.49) and 26.0% ( p = 0.03) for 30 and 60 min tMCAO, respectively, at the rat-equivalent dose of 10 nMole/g, but not at the previously reported 3 nMole/g in mice. Dose translation is thus critical when preclinical experiments are conducted in new species.
Environmental enrichment enhances synaptic plasticity by internalization of striatal dopamine transporters
Authors: Kim Myung-Sun , Yu Ji Hea , Kim Chul Hoon , Choi Jae Yong , Seo Jung Hwa , Lee Min-Young , Yi Chi Hoon , Choi Tae Hyun , Ryu Young Hoon , Lee Jong Eun , Lee Bae Hwan , Kim Hyongbum , Cho Sung-Rae
Published: December 2015

Environmental enrichment (EE) with a complex combination of physical, cognitive and social stimulations enhances synaptic plasticity and behavioral function. However, the mechanism remains to be elucidated in detail. We aimed to investigate dopamine-related synaptic plasticity underlying functional improvement after EE. For this, six-week-old CD-1 mice were randomly allocated to EE or standard conditions for two months. EE significantly enhanced behavioral functions such as rotarod and ladder walking tests. In a [18F]FPCIT positron emission tomography scan, binding values of striatal DAT were significantly decreased approximately 18% in the EE mice relative to the control mice. DAT inhibitor administrated to establish the relationship of the DAT down-regulation to the treatment effects also improved rotarod performances, suggesting that DAT inhibition recapitulated EE-mediated treatment benefits. Next, EE-induced internalization of DAT was confirmed using a surface biotinylation assay. In situ proximity ligation assay and immunoprecipitation demonstrated that EE significantly increased the phosphorylation of striatal DAT as well as the levels of DAT bound with protein kinase C (PKC). In conclusion, we suggest that EE enables phosphorylation of striatal DAT via a PKC-mediated pathway and causes DAT internalization. This is the first report to suggest an EE-mediated mechanism of synaptic plasticity by internalization of striatal DAT.
Pharmacologic manipulation of lysosomal enzyme transport across the blood–brain barrier
Authors: Urayama Akihiko , Grubb Jeffrey H , Sly William S , Banks William A
Published: December 2015

The adult blood–brain barrier, unlike the neonatal blood–brain barrier, does not transport lysosomal enzymes into brain, making enzyme replacement therapy ineffective in treating the central nervous system symptoms of lysosomal storage diseases. However, enzyme transport can be re-induced with alpha-adrenergics. Here, we examined agents that are known to alter the blood–brain barrier transport of large molecules or to induce lysosomal enzyme transport across the blood–brain barrier ((±)epinephrine, insulin, retinoic acid, and lipopolysaccharide) in 2-week-old and adult mice. In 2-week-old adolescent mice, all these pharmacologic agents increased brain and heart uptake of phosphorylated human β-glucuronidase. In 8-week-old adult mice, manipulations with (±)epinephrine, insulin, and retinoic acid were significantly effective on uptake by brain and heart. The increased uptake of phosphorylated human  β-glucuronidase was inhibited by mannose 6-phosphate for the agents (±)epinephrine and retinoic acid and by L-NG-nitroarginine methyl ester for the agent lipopolysaccharide in neonatal and adult mice. An in situ brain perfusion study revealed that retinoic acid directly modulated the transport of phosphorylated human β-glucuronidase across the blood–brain barrier. The present study indicates that there are multiple opportunities to at least transiently induce phosphorylated human β-glucuronidase transport at the adult blood–brain barrier.
The effects of hemodynamic lag on functional connectivity and behavior after stroke
Authors: Siegel Joshua S , Snyder Abraham Z , Ramsey Lenny , Shulman Gordon L , Corbetta Maurizio
Published: December 2015

Stroke disrupts the brain’s vascular supply, not only within but also outside areas of infarction. We investigated temporal delays (lag) in resting state functional magnetic resonance imaging signals in 130 stroke patients scanned two weeks, three months and 12 months post stroke onset. Thirty controls were scanned twice at an interval of three months. Hemodynamic lag was determined using cross-correlation with the global gray matter signal. Behavioral performance in multiple domains was assessed in all patients. Regional cerebral blood flow and carotid patency were assessed in subsets of the cohort using arterial spin labeling and carotid Doppler ultrasonography. Significant hemodynamic lag was observed in 30% of stroke patients sub-acutely. Approximately 10% of patients showed lag at one-year post-stroke. Hemodynamic lag corresponded to gross aberrancy in functional connectivity measures, performance deficits in multiple domains and local and global perfusion deficits. Correcting for lag partially normalized abnormalities in measured functional connectivity. Yet post-stroke FC–behavior relationships in the motor and attention systems persisted even after hemodynamic delays were corrected. Resting state fMRI can reliably identify areas of hemodynamic delay following stroke. Our data reveal that hemodynamic delay is common sub-acutely, alters functional connectivity, and may be of clinical importance.
Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease
Authors: Martino Adami Pamela V , Quijano Celia , Magnani Natalia , Galeano Pablo , Evelson Pablo , Cassina Adriana , Do Carmo Sonia , Leal María C , Castaño Eduardo M , Cuello A Claudio , Morelli Laura
Published: December 2015

Synaptic bioenergetic deficiencies may be associated with early Alzheimer's disease (AD). To explore this concept, we assessed pre-synaptic mitochondrial function in hemizygous (+/−)TgMcGill-R-Thy1-APP rats. The low burden of Aβ and the wide array of behavioral and cognitive impairments described in 6-month-old hemizygous TgMcGill-R-Thy1-APP rats (Tg(+/−)) support their use to investigate synaptic bioenergetics deficiencies described in subjects with early Alzheimer's disease (AD). In this report, we show that pre-synaptic mitochondria from Tg(+/−) rats evidence a decreased respiratory control ratio and spare respiratory capacity associated with deficits in complex I enzymatic activity. Cognitive impairments were prevented and bioenergetic deficits partially reversed when Tg(+/−) rats were fed a nutritionally complete diet from weaning to 6-month-old supplemented with pyrroloquinoline quinone, a mitochondrial biogenesis stimulator with antioxidant and neuroprotective effects. These results provide evidence that, as described in AD brain and not proven in Tg mice models with AD-like phenotype, the mitochondrial bioenergetic capacity of synaptosomes is not conserved in the Tg(+/−) rats. This animal model may be suitable for understanding the basic biochemical mechanisms involved in early AD.
Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response
Authors: Hubbard Nicholas A , Turner Monroe , Hutchison Joanna L , Ouyang Austin , Strain Jeremy , Oasay Larry , Sundaram Saranya , Davis Scott , Remington Gina , Brigante Ryan , Huang Hao , Hart John , Frohman Teresa , Frohman Elliot , Biswal Bharat B , Rypma Bart
Published: December 2015

Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences.
Quantifying fluctuations of resting state networks using arterial spin labeling perfusion MRI
Authors: Dai Weiying , Varma Gopal , Scheidegger Rachel , Alsop David C
Published: December 2015

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to investigate spontaneous low-frequency signal fluctuations across brain resting state networks. However, BOLD only provides relative measures of signal fluctuations. Arterial Spin Labeling (ASL) MRI holds great potential for quantitative measurements of resting state network fluctuations. This study systematically quantified signal fluctuations of the large-scale resting state networks using ASL data from 20 healthy volunteers by separating them from global signal fluctuations and fluctuations caused by residual noise. Global ASL signal fluctuation was 7.59% ± 1.47% relative to the ASL baseline perfusion. Fluctuations of seven detected resting state networks vary from 2.96% ± 0.93% to 6.71% ± 2.35%. Fluctuations of networks and residual noise were 6.05% ± 1.18% and 6.78% ± 1.16% using 4-mm resolution ASL data applied with Gaussian smoothing kernel of 6mm. However, network fluctuations were reduced by 7.77% ± 1.56% while residual noise fluctuation was markedly reduced by 39.75% ± 2.90% when smoothing kernel of 12 mm was applied to the ASL data. Therefore, global and network fluctuations are the dominant structured noise sources in ASL data. Quantitative measurements of resting state networks may enable improved noise reduction and provide insights into the function of healthy and diseased brain.
Dynamic cerebral autoregulation following acute ischaemic stroke: Comparison of transcranial Doppler and magnetic resonance imaging techniques
Authors: Panerai Ronney B , Jara José L , Saeed Nazia P , Horsfield Mark A , Robinson Thompson G
Published: December 2015

Novel MRI-based dynamic cerebral autoregulation (dCA) assessment enables the estimation of both global and spatially discriminated autoregulation index values. Before exploring this technique for the evaluation of focal dCA in acute ischaemic stroke (AIS) patients, it is necessary to compare global dCA estimates made using both TCD and MRI. Both techniques were used to study 11 AIS patients within 48 h of symptom onset, and nine healthy controls. dCA was assessed by the rate of return of CBFV ( Rturn) following a sudden drop induced by the thigh cuff manoeuvre. No significant between-hemisphere differences were seen in controls using either the TCD or MRI technique. Inter-hemisphere averaged Rturn values were not different between TCD (1.89 ± 0.67%/s) and MRI (2.07 ± 0.60%/s) either. In patients, there were no differences between the affected and unaffected hemispheres whether assessed by TCD ( Rturn 0.67 ± 0.72 vs. 0.98 ± 1.09%/s) or MRI (0.55 ± 1.51 vs. 1.63 ± 0.63%/s). Rturn for both TCD and MRI was impaired in AIS patients compared to controls in both unaffected and affected hemispheres (ANOVA, p = 0.00005). These findings pave the way for wider use of MRI for dCA assessment in health and disease.
Ion channel networks in the control of cerebral blood flow
Authors: Longden Thomas A , Hill-Eubanks David C , Nelson Mark T
Published: December 2015

One hundred and twenty five years ago, Roy and Sherrington made the seminal observation that neuronal stimulation evokes an increase in cerebral blood flow.1 Since this discovery, researchers have attempted to uncover how the cells of the neurovascular unit—neurons, astrocytes, vascular smooth muscle cells, vascular endothelial cells and pericytes—coordinate their activity to control this phenomenon. Recent work has revealed that ionic fluxes through a diverse array of ion channel species allow the cells of the neurovascular unit to engage in multicellular signaling processes that dictate local hemodynamics.

In this review we center our discussion on two major themes: (1) the roles of ion channels in the dynamic modulation of parenchymal arteriole smooth muscle membrane potential, which is central to the control of arteriolar diameter and therefore must be harnessed to permit changes in downstream cerebral blood flow, and (2) the striking similarities in the ion channel complements employed in astrocytic endfeet and endothelial cells, enabling dual control of smooth muscle from either side of the blood–brain barrier. We conclude with a discussion of the emerging roles of pericyte and capillary endothelial cell ion channels in neurovascular coupling, which will provide fertile ground for future breakthroughs in the field.
High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion
Authors: Zuloaga Kristen L , Johnson Lance A , Roese Natalie E , Marzulla Tessa , Zhang Wenri , Nie Xiao , Alkayed Farah N , Hong Christine , Grafe Marjorie R , Pike Martin M , Raber Jacob , Alkayed Nabil J
Published: December 2015

Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology.
Video training and certification program improves reliability of postischemic neurologic deficit measurement in the rat
Authors: Taninishi Hideki , Pearlstein Molly , Sheng Huaxin , Izutsu Miwa , Chaparro Rafael E , Goldstein Larry B , Warner David S
Published: December 2015

Scoring systems are used to measure behavioral deficits in stroke research. Video-assisted training is used to standardize stroke-related neurologic deficit scoring in humans. We hypothesized that a video-assisted training and certification program can improve inter-rater reliability in assessing neurologic function after middle cerebral artery occlusion in rats. Three expert raters scored neurologic deficits in post-middle cerebral artery occlusion rats using three published systems having different complexity levels (3, 18, or 48 points). The system having the highest point estimate for the correlation between neurologic score and infarct size was selected to create a video-assisted training and certification program. Eight trainee raters completed the video-assisted training and certification program. Inter-rater agreement (κ score) and agreement with expert consensus scores were measured before and after video-assisted training and certification program completion. The 48-point system correlated best with infarct size. Video-assisted training and certification improved agreement with expert consensus scores (pretraining = 65 ± 10, posttraining = 87 ± 14, 112 possible scores, P < 0.0001), median number of trainee raters with scores within ±2 points of the expert consensus score (pretraining = 4, posttraining = 6.5, P < 0.01), categories with κ > 0.4 (pretraining = 4, posttraining = 9), and number of categories with an improvement in the κ score from pretraining to posttraining (n = 6). Video-assisted training and certification improved trainee inter-rater reliability and agreement with expert consensus behavioral scores in rats after middle cerebral artery occlusion. Video-assisted training and certification may be useful in multilaboratory preclinical studies.
4D flow MRI for intracranial hemodynamics assessment in Alzheimer’s disease
Authors: Rivera-Rivera Leonardo A , Turski Patrick , Johnson Kevin M , Hoffman Carson , Berman Sara E , Kilgas Phillip , Rowley Howard A , Carlsson Cynthia M , Johnson Sterling C , Wieben Oliver
Published: December 2015

Cerebral blood flow, arterial pulsation, and vasomotion play important roles in the transport of waste metabolites out of the brain. Impaired vasomotion results in reduced driving force for the perivascular/glymphatic clearance of beta-amyloid. Noninvasive cerebrovascular characteristic features that potentially assess these transport mechanisms are mean blood flow (MBF) and pulsatility index (PI). In this study, 4D flow MRI was used to measure intra-cranial flow features, particularly MBF, PI, resistive index (RI) and cross-sectional area in patients with Alzheimer’s disease (AD), mild cognitive impairment and in age matched and younger cognitively healthy controls. Three-hundred fourteen subjects participated in this study. Volumetric, time-resolved phase contrast (PC) MRI data were used to quantify hemodynamic parameters from 11 vessel segments. Anatomical variants of the Circle of Willis were also cataloged. The AD population reported a statistically significant decrease in MBF and cross-sectional area, and also an increase in PI and RI compared to age matched cognitively healthy control subjects. The 4D flow MRI technique used in this study provides quantitative measurements of intracranial vessel geometry and the velocity of flow. Cerebrovascular characteristics features of vascular health such as pulsatility index can be extracted from the 4D flow MRI data.
Molecular pathophysiology of cerebral edema
Authors: Stokum Jesse A , Gerzanich Volodymyr , Simard J Marc
Published: December 2015

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema.
The major cerebral arteries proximal to the Circle of Willis contribute to cerebrovascular resistance in humans
Authors: Warnert Esther AH , Hart Emma C , Hall Judith E , Murphy Kevin , Wise Richard G
Published: December 2015

Cerebral autoregulation ensures constant cerebral blood flow during periods of increased blood pressure by increasing cerebrovascular resistance. However, whether this increase in resistance occurs at the level of major cerebral arteries as well as at the level of smaller pial arterioles is still unknown in humans. Here, we measure cerebral arterial compliance, a measure that is inversely related to cerebrovascular resistance, with our novel non-invasive magnetic resonance imaging-based measurement, which employs short inversion time pulsed arterial spin labelling to map arterial blood volume at different phases of the cardiac cycle. We investigate the differential response of the cerebrovasculature during post exercise ischemia (a stimulus which leads to increased cerebrovascular resistance because of increases in blood pressure and sympathetic outflow). During post exercise ischemia in eight normotensive men (30.4 ± 6.4 years), cerebral arterial compliance decreased in the major cerebral arteries at the level of and below the Circle of Willis, while no changes were measured in arteries above the Circle of Willis. The reduction in arterial compliance manifested as a reduction in the arterial blood volume during systole. This study provides the first evidence that in humans the major cerebral arteries may play an important role in increasing cerebrovascular resistance.
Role of prostacyclin signaling in endothelial production of soluble amyloid precursor protein-α in cerebral microvessels
Authors: He Tongrong , Santhanam Anantha Vijay R , Lu Tong , d'Uscio Livius V , Katusic Zvonimir S
Published: December 2015

We tested hypothesis that activation of the prostacyclin (PGI2) receptor (IP receptor) signaling pathway in cerebral microvessels plays an important role in the metabolism of amyloid precursor protein (APP). In human brain microvascular endothelial cells activation of IP receptor with the stable analogue of PGI2, iloprost, stimulated expression of amyloid precursor protein and a disintegrin and metalloprotease 10 (ADAM10), resulting in an increased production of the neuroprotective and anticoagulant molecule, soluble APPα (sAPPα). Selective agonist of IP receptor, cicaprost, and adenylyl cyclase activator, forskolin, also enhanced expression of amyloid precursor protein and ADAM10. Notably, in cerebral microvessels of IP receptor knockout mice, protein levels of APP and ADAM10 were reduced. In addition, iloprost increased protein levels of peroxisome proliferator-activated receptor δ (PPARδ) in human brain microvascular endothelial cells. PPARδ-siRNA abolished iloprost-augmented protein expression of ADAM10. In contrast, GW501516 (a selective agonist of PPARδ) upregulated ADAM10 and increased production of sAPPα. Genetic deletion of endothelial PPARδ (ePPARδ−/−) in mice significantly reduced cerebral microvascular expression of ADAM10 and production of sAPPα. In vivo treatment with GW501516 increased sAPPα content in hippocampus of wild type mice but not in hippocampus of ePPARδ−/− mice. Our findings identified previously unrecognized role of IP-PPARδ signal transduction pathway in the production of sAPPα in cerebral microvasculature.
Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage
Authors: Hamming Arend M , Wermer Marieke JH , Umesh Rudrapatna S , Lanier Christian , van Os Hine JA , van den Bergh Walter M , Ferrari Michel D , van der Toorn Annette , van den Maagdenberg Arn MJM , Stowe Ann M , Dijkhuizen Rick M
Published: December 2015

Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T2-weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233 mm3) than in the no-SD group (29 ± 54 mm3) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.
Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury
Authors: Helmy Adel , Guilfoyle Mathew R , Carpenter Keri LH , Pickard John D , Menon David K , Hutchinson Peter J
Published: December 2015

Interleukin-1 receptor antagonist (IL1ra) has demonstrated efficacy in a wide range of animal models of neuronal injury. We have previously published a randomised controlled study of IL1ra in human severe TBI, with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines. In this study, we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain. We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury, particularly in samples from the first 48 h following injury. The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space. Chemokines related to recruitment of macrophages from the plasma compartment (MCP-1) and biasing towards a M1 microglial phenotype (GM-CSF, IL1) are increased in patient samples in the rhIL1ra-treated patients. In control patients, cytokines and chemokines biased to a M2 microglia phenotype (IL4, IL10, MDC) are relatively increased. This pattern of response suggests that a simple classification of IL1ra as an ‘anti-inflammatory’ cytokine may not be appropriate and highlights the importance of the microglial response to injury.
Quantitative assessment of microvasculopathy in arcAβ mice with USPIO-enhanced gradient echo MRI
Authors: Klohs Jan , Deistung Andreas , Ielacqua Giovanna D , Seuwen Aline , Kindler Diana , Schweser Ferdinand , Vaas Markus , Kipar Anja , Reichenbach Jürgen R , Rudin Markus
Published: December 2015

Magnetic resonance imaging employing administration of iron oxide-based contrast agents is widely used to visualize cellular and molecular processes in vivo. In this study, we investigated the ability of [Formula: see text] and quantitative susceptibility mapping to quantitatively assess the accumulation of ultrasmall superparamagnetic iron oxide (USPIO) particles in the arcAβ mouse model of cerebral amyloidosis. Gradient-echo data of mouse brains were acquired at 9.4 T after injection of USPIO. Focal areas with increased magnetic susceptibility and [Formula: see text] values were discernible across several brain regions in 12-month-old arcAβ compared to 6-month-old arcAβ mice and to non-transgenic littermates, indicating accumulation of particles after USPIO injection. This was concomitant with higher [Formula: see text] and increased magnetic susceptibility differences relative to cerebrospinal fluid measured in USPIO-injected compared to non-USPIO-injected 12-month-old arcAβ mice. No differences in [Formula: see text] and magnetic susceptibility were detected in USPIO-injected compared to non-injected 12-month-old non-transgenic littermates. Histological analysis confirmed focal uptake of USPIO particles in perivascular macrophages adjacent to small caliber cerebral vessels with radii of 2–8 µm that showed no cerebral amyloid angiopathy. USPIO-enhanced [Formula: see text] and quantitative susceptibility mapping constitute quantitative tools to monitor such functional microvasculopathies.
Headaches in patients with previous head injuries: A population-based historical cohort study (HUNT)
Authors: Nordhaug Lena Hoem , Vik Anne , Hagen Knut , Stovner Lars Jacob , Pedersen Torunn , Gravdahl Gøril Bruvik , Linde Mattias
Published: December 2015

Background

Headache attributed to head injury is claimed to be among the most common secondary headache disorders, yet available epidemiological evidence is scarce. We evaluated the prevalence of headache among individuals previously exposed to head injury by a comparison to an uninjured control group.

Methods

This population-based historical cohort study used data from hospital records on previous exposure to head injury linked to a large epidemiological survey with data on headache occurrence. Participants without head injury, according to hospital records, were used as controls. The head injuries were classified according to the Head Injury Severity Scale (HISS) and the International Classification of Headache Disorders (ICHD-3 beta). Binary logistic regression was performed to investigate the association between headache and head injury, controlling for potential confounders.

Results

The exposed group consisted of 940 individuals and the control group of 38,751 individuals. In the multivariate analyses, adjusting for age, sex, anxiety, depression and socioeconomic status, there were significant associations between mild head injury and any headache, migraine, chronic daily headache and medication overuse headache.

Conclusion

Headache was more likely among individuals previously referred to a hospital for a mild head injury compared to uninjured controls.
Screen time exposure and reporting of headaches in young adults: A cross-sectional study
Authors: Montagni Ilaria , Guichard Elie , Carpenet Claire , Tzourio Christophe , Kurth Tobias
Published: December 2015

Objective

The objective of this article is to investigate whether excessive screen time exposure is associated with non-migraine headache and migraine in young adults.

Background

Increased levels of television time have been associated with increased risk of headache. However, time spent using newer electronic devices with a screen (smartphone, tablet) has not been examined yet.

Methods

We conducted a cross-sectional study among 4927 participants of the French i-Share cohort. Demographic characteristics, screen time exposure (computers, tablets, smartphones and television) as well as headache/migraine symptoms were recorded in a standardized questionnaire. Multinomial logistic regression models were used to evaluate the association between screen time exposure and headache status.

Results

Participants had a mean age of 20.8 years and 75.5% were female. The multivariable model showed that students in the highest screen time exposure quintile had an increased risk for migraine. The odds ratio (OR) (95% confidence interval (CI)) was 1.37 (1.14 to 1.66) for migraine when compared with students without headache and with low screen time exposure. This association was somewhat stronger for migraine without aura (OR = 1.50, 95% CI 1.19 to 1.89). We found no significant association between screen time exposure and non-migraine headache.

Conclusion

High levels of screen time exposure are associated with migraine in young adults. No significant association was found with non-migraine headache.
Refractory chronic spontaneous urticaria and permanent atrial fibrillation associated with dental infection: Mere coincidence or something more to it?
Authors: Kasperska-Zajac Alicja , Grzanka Alicja , Kowalczyk Jacek , Wyszyńska-Chłap Magdalena , Lisowska Grażyna , Kasperski Jacek , Jarząb Jerzy , Misiołek Maciej , Kalarus Zbigniew
Published: December 2015

Controversy surrounds the role of dental infection/inflammation in the oral cavity in chronic spontaneous urticaria (CSU) and atrial fibrillation (AF), which is mainly due to scarce literature in this area. Therefore, this case report and review of literature illustrate a possible association between the acute-phase response (APR) and clinical conditions, such as CSU and dental infection/inflammation of oral cavity and AF.

We describe a 36-year-old man with an 8-year history of difficult-to-treat, uncontrolled CSU, co-existent with dental infection/inflammatory processes of oral cavity and permanent atrial fibrillation (AF). In the presented case, the most likely triggering or aggravating/maintaining factor of the symptoms was the inflammation/dental infection of the oral cavity because of rapid reduction of the urticarial symptoms, drug doses, and serum CRP levels after the dental therapy. Dental treatment may have a beneficial effect on the systemic inflammatory response, reducing/normalizing the circulating levels of APR markers. APR activation appears to worsen CSU course, early identification and treatment of infectious/inflammatory foci in the oral cavity would form the mainstay of supportive therapy for CU probably through reduction of the systemic inflammatory burden. APR associated with infectious/inflammatory foci in the oral cavity could be taken into account as a predisposing agents to AF.
Analysis of natural fiber polymer composites: Effects of alkaline treatment on sound absorption
Authors: Jayamani Elammaran , Hamdan Sinin , Bakri Muhammad Khusairy Bin , Kok Heng Soon , Rahman Md Rezaur , Kakar Akshay
Published: December 2015

This study is focused on the development of sound absorbing materials based on natural fiber polymer composites. The natural fibers were modified through the alkaline treatment and the natural fiber polymer composites were fabricated using hot and cold compression hydraulic press machine. The sound absorption coefficients of the composites were measured using two-microphone transfer function impedance tube method. Characterizations of the natural fiber polymer composites were analyzed using scanning electron microscope and Fourier transform infrared spectroscopy. It was found that in all measured composites, the sound absorption coefficients increased as the frequency increased. Also, as the fiber loading increased, the sound absorption coefficients of the natural fiber polymer composites were increased. It was found that the alkaline treated fiber reinforced composites increased the sound absorption coefficients due to removal of impurities and change in the structure of composites. The alkaline treatment of fibers showed better adhesion interface between fiber and polymer as compared to untreated fibers. This can be seen clearly under morphological and spectral studies of the natural fiber polymer composites.
Evaluation of the economic feasibility of a processing plant for steelmaking slag
Authors: Gonçalves Deyvid RR , Fontes Wanna C , Mendes Julia C , Silva Guilherme JB , Peixoto Ricardo AF
Published: December 2015

The utilisation of steelmaking slag as recycled aggregate for concretes is a widely investigated solution for mitigating the expenditure and environmental impacts of its storage. The Brazilian steel industry is investing in research and slag reprocessing practices, aiming to reuse most of its metallic fraction and properly allocate the non-metallic fraction, saving energy and reducing mining impacts. Research results demonstrate the technical and environmental feasibility of steel slag aggregates for civil construction. However, it is essential to evaluate whether the processing of the slag is economically feasible for this purpose. Economic analysis of the processing of steel slag was conducted through simulation – Monte Carlo method – in which it is possible to determine the risks and uncertainties inherent to the project. The costs that comprise the proposed project, from design through construction and operation itself, were estimated at US$2.8 million. The result of the simulation indicates economic feasibility of the project with 98% certainty, and an estimated profit of around 42%.
The Association Between Social Support and Stages of Change in Survivors of Intimate Partner Violence
Authors: Zapor Heather , Wolford-Clevenger Caitlin , Johnson Dawn M.
Published: December 2015

For survivors of intimate partner violence (IPV), it is often difficult to take steps to establish safety and obtain a violence free life. Researchers have applied stage of change theory to aid in understanding the experience of survivors, as well as, the factors that can help women who desire to make changes in or break free from a violent relationship. Social support is one factor that can be helpful to IPV survivors who are attempting to make changes in their relationship. The purpose of the current study was to examine the differences in social support experienced by women who are at varying points in the process of change. Shelter residents ( N = 191) participated in this cross-sectional non-experimental study. Analyses demonstrated five distinct clusters or profiles of change among study participants and were labeled by the authors as follows: preparticipation, decision making, engagement, ambivalent, and action. All forms of social support (i.e., structural, functional, and satisfaction) were generally higher for individuals more engaged in the process of change. More specifically, differences were noted between the action and decision-making clusters and the engagement and decision-making clusters. These findings suggest that it is vital that clinicians working with survivors of IPV not only assess but also tailor interventions to meet survivors where they are in the process of change. Further, interventions that foster survivors’ abilities to develop reliable and satisfying social support networks will be beneficial for survivors of IPV.
Breastfeeding Duration and Authoritative Feeding Practices in First-Time Mothers
Authors: Jansen Elena , Mallan Kimberley M. , Byrne Rebecca , Daniels Lynne A. , Nicholson Jan M.
Published: December 2015

Background:

Longer breastfeeding duration appears to have a protective effect against childhood obesity. This effect may be partially mediated by maternal feeding practices during the first years of life. However, the few studies that have examined links between breastfeeding duration and subsequent feeding practices have yielded conflicting results.

Objective:

Using a large sample of first-time mothers and a newly validated, comprehensive measure of maternal feeding (the Feeding Practices and Structure Questionnaire), this study examined associations between breastfeeding duration and maternal feeding practices at child age 24 months.

Methods:

Mothers (n = 458) enrolled in the NOURISH trial provided data on breastfeeding at child age 4, 14, and 24 months, and on feeding practices at 24 months. Structural equation modeling was used to examine associations between breastfeeding duration and 5 nonresponsive and 4 structure-related “authoritative” feeding practices, adjusting for a range of maternal and child characteristics.

Results:

The model showed acceptable fit (χ2/df = 1.68; root mean square error of approximation = .04, comparative fit index = .91, and Tucker-Lewis index = .89) and longer breastfeeding duration was negatively associated with 4 out of 5 nonresponsive feeding practices and positively associated with 3 out of 4 structure-related feeding practices. Overall, these results suggest that mothers who breastfeed longer reported using more appropriate feeding practices.

Conclusion:

These data demonstrate an association between longer breastfeeding duration and authoritative feeding practices characterized by responsiveness and structure, which may partly account for the apparent protective effect of breastfeeding on childhood obesity.
What Does Really Matter in Technology Adoption and Use? A CCO Approach
Authors: Martine Thomas , Cooren François , Bénel Aurélien , Zacklad Manuel
Published: December 2015

Building on Orlikowski’s reflections on sociomateriality, this article argues that we have to stop separating the material and the social to be able to precisely account for what matters in technology adoption and use, and that one way to do this is to take people’s matters of concern seriously. This means two things: taking into account all the matters of concern that come to express themselves in conversations (whether related to tools, rules, documents, principles, etc.) and not just the people who voice them, and showing how some of these concerns start mattering more than others by connecting with other matters of concern. To demonstrate the theoretical and empirical value of this approach, we analyze two interactional episodes taken from our longitudinal study of the introduction of a wiki at the French National Agency for Radioactive Waste Management.