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Journal of Cerebral Blood Flow and Metabolism

Bastian Cheng, Philipp Dietzmann, Robert Schulz, Marlene Boenstrup, Lutz Krawinkel, Jens Fiehler, Christian Gerloff, Götz Thomalla
Following acute ischemic stroke, isolated subcortical lesions induce gray matter atrophy in anatomically connected, yet distant cortical brain regions. We expand on previous studies by analyzing cortical thinning in contralesional, homologous regions indirectly linked to primary stroke lesions via ipsilesional cortical areas. For this purpose, stroke patients were serially studied by magnetic resonance imaging (diffusion tensor imaging and high-resolution anatomical imaging) in the acute (days 3-5) and late chronic stage one year after stroke...
February 20, 2019: Journal of Cerebral Blood Flow and Metabolism
Tsubasa Tomoto, Jonathan Riley, Marcel Turner, Rong Zhang, Takashi Tarumi
Age is the strongest risk factor for cerebrovascular disease; however, age-related changes in cerebrovascular function are still not well understood. The objective of this study was to measure cerebral vasomotor reactivity (CVMR) during hypo- and hypercapnia across the adult lifespan. One hundred fifty-three healthy participants (21-80 years) underwent measurements of cerebral blood flow velocity (CBFV) via transcranial Doppler, mean arterial pressure (MAP) via plethysmograph, and end-tidal CO2 (EtCO2 ) via capnography during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia)...
February 15, 2019: Journal of Cerebral Blood Flow and Metabolism
James E Orfila, Robert M Dietz, Krista M Rodgers, Andra Dingman, Olivia P Patsos, Ivelisse Cruz-Torres, Himmat Grewal, Frank Strnad, Christian Schroeder, Paco S Herson
Ischemic stroke is a leading cause of death worldwide and clinical data suggest that children may recover from stroke better than adults; however, supporting experimental data are lacking. We used our novel mouse model of experimental juvenile ischemic stroke (MCAO) to characterize age-specific cognitive dysfunction following ischemia. Juvenile and adult mice subjected to 45-min MCAO, and extracellular field recordings of CA1 neurons were performed to assess hippocampal synaptic plasticity changes after MCAO, and contextual fear conditioning was performed to evaluate memory and biochemistry used to analyze Nogo-A expression...
February 14, 2019: Journal of Cerebral Blood Flow and Metabolism
Alexander Seiler, Arne Lauer, Ralf Deichmann, Ulrike Nöth, Eva Herrmann, Joachim Berkefeld, Oliver C Singer, Waltraud Pfeilschifter, Johannes C Klein, Marlies Wagner
As a determinant of the progression rate of the ischaemic process in acute large-vessel stroke, the degree of collateralization is a strong predictor of the clinical outcome after reperfusion therapy and may influence clinical decision-making. Therefore, the assessment of leptomeningeal collateralization is of major importance. The purpose of this study was to develop and evaluate a quantitative and observer-independent method for assessing leptomeningeal collateralization in acute large-vessel stroke based on signal variance characteristics in T2*-weighted dynamic susceptibility contrast (DSC) perfusion-weighted MR imaging (PWI)...
February 13, 2019: Journal of Cerebral Blood Flow and Metabolism
Murat Bilgel, Lori Beason-Held, Yang An, Yun Zhou, Dean F Wong, Susan M Resnick
Surrogates of neuronal activity, typically measured by regional cerebral blood flow (rCBF) or glucose metabolism, can be estimated from dynamic amyloid PET imaging. Using data for 149 participants (345 visits) from the Baltimore Longitudinal Study of Aging, we assessed whether the average of early amyloid frames (EA) and R1 computed from dynamic 11 C-Pittsburgh compound B (PiB) PET can serve as surrogates of rCBF computed from 15 O-H2 O-PET. R1 had the highest longitudinal test-retest reliability. Interquartile range (IQR) of cross-sectional Pearson correlations with rCBF was 0...
February 12, 2019: Journal of Cerebral Blood Flow and Metabolism
Yohan Boillat, Lijing Xin, Wietske van der Zwaag, Rolf Gruetter
Negative blood oxygenation-level dependent (BOLD) signal observed during task execution in functional magnetic resonance imaging (fMRI) can be caused by different mechanisms, such as a blood-stealing effect or neuronal deactivation. Electrophysiological recordings showed that neuronal deactivation underlies the negative BOLD observed in the occipital lobe during visual stimulation. In this study, the metabolic demand of such a response was studied by measuring local metabolite concentration changes during a visual checkerboard stimulation using functional magnetic resonance spectroscopy (fMRS) at 7 Tesla...
February 12, 2019: Journal of Cerebral Blood Flow and Metabolism
Christiaan Hendrik Bas van Niftrik, Martina Sebök, Giovanni Muscas, Marco Piccirelli, Carlo Serra, Niklaus Krayenbühl, Athina Pangalu, Oliver Bozinov, Andreas Luft, Christoph Stippich, Luca Regli, Jorn Fierstra
The clinical significance of ipsilateral thalamic diaschisis (ITD) occurring after stroke is unknown. To characterize ITD, we investigate its hemodynamic, structural, and clinical implications. A single-institution prospective cross-sectional study was conducted using 28 symptomatic cerebrovascular steno-occlusive patients undergoing both BOLD-CVR and Diamox-challenged 15 (O)-H2 O-PET. Follow-up was at least three months. In addition, 15 age-matched healthy subjects were included. ITD was diagnosed based on a BOLD-CVR thalamic asymmetry index (TAI) > +2 standard deviations from healthy subjects...
February 12, 2019: Journal of Cerebral Blood Flow and Metabolism
Zhemin Huang, Chengfeng Jiang, Ling Li, Qian Xu, Jingjie Ge, Ming Li, Yihui Guan, Jianjun Wu, Jian Wang, Chuantao Zuo, Huan Yu, Ping Wu
Striatal dopamine transporter (DAT) deficiency and abnormal expression of Parkinson's disease (PD)-related pattern (PDRP) have been observed in patients with idiopathic REM sleep behavior disorder (IRBD). This study aimed to investigate the correlations between these two measures with comparison to PD using a dual tracer imaging design. Age-matched 37 IRBD patients, 86 PD patients, and 15 control subjects underwent concurrent PET scans with 11 C-CFT to quantify dopaminergic dysfunction and 18 F-FDG to quantify PDRP expression...
February 10, 2019: Journal of Cerebral Blood Flow and Metabolism
Audrey P Fan, Ahmed A Khalil, Jochen B Fiebach, Greg Zaharchuk, Arno Villringer, Kersten Villringer, Claudine J Gauthier
Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients...
February 7, 2019: Journal of Cerebral Blood Flow and Metabolism
Andreas Stadlbauer, Stefan Oberndorfer, Max Zimmermann, Bertold Renner, Michael Buchfelder, Gertraud Heinz, Arnd Doerfler, Andrea Kleindienst, Karl Roessler
Treating recurrent glioblastoma (GB) is one of the challenges in modern neurooncology. Hypoxia, neovascularization, and energy metabolism are of crucial importance for therapy failure and recurrence. Twenty-one patients with initially untreated GB who developed recurrence were examined with a novel MRI approach for noninvasive visualization of the tumor microenvironment (TME). Imaging biomarker information about oxygen metabolism (mitochondrial oxygen tension) and neovascularization (microvascular density and type) were fused for classification of five different TME compartments: necrosis, hypoxia with/without neovascularization, oxidative phosphorylation, and glycolysis...
February 7, 2019: Journal of Cerebral Blood Flow and Metabolism
Andrea M Herrmann, Stephan Meckel, Matthew J Gounis, Leona Kringe, Edith Motschall, Christoph Mülling, Johannes Boltze
Neuroendovascular procedures have led to breakthroughs in the treatment of ischemic stroke, intracranial aneurysms, and intracranial arteriovenous malformations. Due to these substantial successes, there is continuous development of novel and refined therapeutic approaches. Large animal models feature various conceptual advantages in translational research, which makes them appealing for the development of novel endovascular treatments. However, the availability and role of large animal models have not been systematically described so far...
February 7, 2019: Journal of Cerebral Blood Flow and Metabolism
Zhengxi Li, Meng Wei, Haiyan Lyu, Kang Huo, Liang Wang, Meng Zhang, Hua Su
Cognitive impairment occurs in stroke and hip fracture patients. In mice, bone fracture (BF) exacerbates stroke-related neuronal damage and sensorimotor dysfunction. We hypothesize that BF exacerbates post-stroke cognitive impairment. Adult mice were randomly assigned into BF, stroke, BF+stroke (BF 6 h before stroke), and control (sham operated) groups. Memory function was evaluated weekly for eight weeks by Y maze test and at eight weeks post-surgeries by novel object recognition (NOR) test. The neuronal damage and inflammation in hippocampus were analyzed three days and eight weeks after the surgeries...
January 22, 2019: Journal of Cerebral Blood Flow and Metabolism
Gabriel Broocks, Fabian Flottmann, Uta Hanning, Gerhard Schön, Peter Sporns, Jens Minnerup, Jens Fiehler, Andre Kemmling
Studies evaluating the effect of reperfusion on ischemic edema in acute stroke described conflicting results. Net water uptake (NWU) per brain volume is a new quantitative imaging biomarker of space-occupying ischemic edema, which can be measured in computed tomography (CT). We sought to investigate the effects of vessel recanalization on the formation of ischemic brain edema using quantitative NWU. In this multicenter observational study, acute ischemic stroke patients with a large vessel occlusion (LVO) in the anterior circulation were consecutively screened...
January 10, 2019: Journal of Cerebral Blood Flow and Metabolism
Joel Faustino, Sophorn Chip, Nikita Derugin, Amandine Jullienne, Mary Hamer, Elizabeth Haddad, Oleg Butovsky, Andre Obenaus, Zinaida S Vexler
Stroke is among the top 10 causes of death in children. The developmental stage of the brain is central to stroke pathophysiology. The incidence of childhood arterial ischemic stroke (CAIS) is lower than of perinatal arterial ischemic stroke but the rate of recurrence is strikingly high. Vascular inflammation is seen as major contributor to CAIS but the mechanisms that govern structural-functional basis of vascular abnormalities remain poorly understood. To identify the contribution of immune-neurovascular interactions to CAIS, we established stroke model in postnatal day 21 (P21) mice...
January 10, 2019: Journal of Cerebral Blood Flow and Metabolism
Yutaro Hoshi, Yasuo Uchida, Masanori Tachikawa, Sumio Ohtsuki, Pierre-Olivier Couraud, Takashi Suzuki, Tetsuya Terasaki
Exposure of the brain to high levels of glucocorticoids during ischemia-reperfusion induces neuronal cell death. Oxidative stress alters blood-brain barrier (BBB) function during ischemia-reperfusion, and so we hypothesized that it might impair P-glycoprotein (P-gp)-mediated efflux transport of glucocorticoids at the BBB. Therefore, the purpose of this study was to clarify the molecular mechanism of this putative decrease of P-gp-mediated efflux function. First, we established that H2 O2 treatment of a human in vitro BBB model (hCMEC/D3) reduced both P-gp efflux transport activity and protein expression on the plasma membrane within 20 min...
January 9, 2019: Journal of Cerebral Blood Flow and Metabolism
Pavel Yanev, Katherine Poinsatte, Devon Hominick, Noor Khurana, Kielen R Zuurbier, Marcus Berndt, Erik J Plautz, Michael T Dellinger, Ann M Stowe
The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice...
January 9, 2019: Journal of Cerebral Blood Flow and Metabolism
Aiki Marushima, Melina Nieminen, Irina Kremenetskaia, Roberto Gianni-Barrera, Johannes Woitzik, Georges von Degenfeld, Andrea Banfi, Peter Vajkoczy, Nils Hecht
The myoblast-mediated delivery of angiogenic genes represents a cell-based approach for targeted induction of therapeutic collateralization. Here, we tested the superiority of myoblast-mediated co-delivery of vascular endothelial growth factor-A (VEGF) together with platelet-derived growth factor-BB (PDGF-BB) on transpial collateralization of an indirect encephalomyosynangiosis (EMS) in a model of chronic cerebral ischemia. Mouse myoblasts expressing a reporter gene alone (empty vector), VEGF, PDGF-BB or VEGF and PDGF-BB through a single bi-cistronic vector (VIP) were implanted into the temporalis muscle of an EMS following permanent ipsilateral internal carotid artery occlusion in adult, male C57BL/6N mice...
January 9, 2019: Journal of Cerebral Blood Flow and Metabolism
Susan A Austin, Zvonimir S Katusic
Cerebral amyloid angiopathy (CAA) is present in over half of the elderly population and in 80-90% of Alzheimer's disease (AD) patients. CAA is defined by the deposition of beta amyloid (Aβ) in small cerebral arteries and capillaries. Cardiovascular risk factors are associated with an increased incidence of CAA. We utilized 18-month-old endothelial nitric oxide synthase (eNOS) heterozygous knockout (+/- ) mice, a clinically relevant model of endothelial dysfunction, to examine the role of endothelial nitric oxide (NO) in vascular Aβ accumulation...
January 7, 2019: Journal of Cerebral Blood Flow and Metabolism
Richard S Beard, Brian A Hoettels, Jamie E Meegan, Travis S Wertz, Byeong J Cha, Xiaoyuan Yang, Julia T Oxford, Mack H Wu, Sarah Y Yuan
Inflammation-induced blood-brain barrier (BBB) dysfunction and microvascular leakage are associated with a host of neurological disorders. The tight junction protein claudin-5 (CLDN5) is a crucial protein necessary for BBB integrity and maintenance. CLDN5 is negatively regulated by the transcriptional repressor FOXO1, whose activity increases during impaired insulin/AKT signaling. Owing to an incomplete understanding of the mechanisms that regulate CLDN5 expression in BBB maintenance and dysfunction, therapeutic interventions remain underdeveloped...
December 21, 2018: Journal of Cerebral Blood Flow and Metabolism
Sandeep Sv Golla, Emma E Wolters, Tessa Timmers, Rik Ossenkoppele, Chris Wj van der Weijden, Philip Scheltens, Lothar Schwarte, Mark A Mintun, Michael D Devous, Robert C Schuit, Albert D Windhorst, Adriaan A Lammertsma, Maqsood Yaqub, Bart Nm van Berckel, Ronald Boellaard
[18 F]Flortaucipir is a PET tau tracer used to visualize tau binding in Alzheimer's disease (AD) in vivo. The present study evaluated the performance of several methods to obtain parametric images of [18 F]flortaucipir. One hundred and thirty minutes dynamic PET scans were performed in 10 AD patients and 10 controls. Parametric images were generated using different linearization and basis function approaches. Regional binding potential (BPND ) and volume of distribution (VT ) values obtained from the parametric images were compared with corresponding values derived using the reversible two-tissue compartment model (2T4k_VB )...
December 20, 2018: Journal of Cerebral Blood Flow and Metabolism
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