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Journal of Cerebral Blood Flow and Metabolism

Olivia Kiwanuka, Bo-Michael Bellander, Anders Hånell
When evaluating the design of pre-clinical studies in the field of traumatic brain injury, we found substantial differences compared to phase III clinical trials, which in part may explain the difficulties in translating promising experimental drugs into approved treatments. By using network analysis, we also found cases where a large proportion of the studies evaluating a pre-clinical treatment was performed by inter-related researchers, which is potentially problematic. Subjecting all pre-clinical trials to the rigor of a phase III clinical trial is, however, likely not practically achievable...
May 2018: Journal of Cerebral Blood Flow and Metabolism
Allison M Andrews, Evan M Lutton, Lee A Cannella, Nancy Reichenbach, Roshanak Razmpour, Matthew J Seasock, Steven J Kaspin, Steven F Merkel, Dianne Langford, Yuri Persidsky, Servio H Ramirez
Endothelial cells (ECs) form the basis of the blood-brain barrier (BBB), a physical barrier that selectively restricts transport into the brain. In vitro models can provide significant insight into BBB physiology, mechanisms of human disease pathology, toxicology, and drug delivery. Given the limited availability of primary human adult brain microvascular ECs ( aBMVECs), human fetal tissue offers a plausible alternative source for multiple donors and the opportunity to build syngenic tri-cultures from the same host...
May 2018: Journal of Cerebral Blood Flow and Metabolism
Anna Jablonska, Daniel J Shea, Suyi Cao, Jeff Wm Bulte, Miroslaw Janowski, Konstantinos Konstantopoulos, Piotr Walczak
The loss of oligodendrocytes after stroke is one of the major causes of secondary injury. Glial-restricted progenitors (GRPs) have remylenating potential after intraparenchymal cerebral transplantation. The intraarterial (IA) injection route is an attractive gateway for global brain delivery, but, after IA infusion, naive GRPs fail to bind to the cerebral vasculature. The aim of this study was to test whether overexpression of Very Late Antigen-4 (VLA-4) increases endothelial docking and cerebral homing of GRPs in a stroke model...
May 2018: Journal of Cerebral Blood Flow and Metabolism
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April 2018: Journal of Cerebral Blood Flow and Metabolism
Bistra Iordanova, Alberto Vazquez, Takashi Dy Kozai, Mitsuhiro Fukuda, Seong-Gi Kim
The interhemispheric circuit connecting the left and the right mammalian brain plays a key role in integration of signals from the left and the right side of the body. The information transfer is carried out by modulation of simultaneous excitation and inhibition. Hemodynamic studies of this circuit are inconsistent since little is known about neurovascular coupling of mixed excitatory and inhibitory signals. We investigated the variability in hemodynamic responses driven by the interhemispheric circuit during optogenetic and somatosensory activation...
April 2018: Journal of Cerebral Blood Flow and Metabolism
D Andrew Wilkinson, Richard F Keep, Ya Hua, Guohua Xi
Despite the absence of an intervention shown to improve outcomes in intracerebral hemorrhage, preclinical work has led to a greater understanding of the pathologic pathways of brain injury. Methods targeting hematoma clearance through both macroscopic (surgical) and microscopic (endogenous phagocytosis) means are currently under investigation, with multiple clinical trials ongoing. Macroscopic methods for removal involve both catheter- and endoscope-based therapies to remove the hematoma through minimally invasive surgery...
April 2018: Journal of Cerebral Blood Flow and Metabolism
Melanie-Jane Hannocks, Michelle E Pizzo, Jula Huppert, Tushar Deshpande, N Joan Abbott, Robert G Thorne, Lydia Sorokin
Perivascular compartments surrounding central nervous system (CNS) vessels have been proposed to serve key roles in facilitating cerebrospinal fluid flow into the brain, CNS waste transfer, and immune cell trafficking. Traditionally, these compartments were identified by electron microscopy with limited molecular characterization. Using cellular markers and knowledge on cellular sources of basement membrane laminins, we here describe molecularly distinct compartments surrounding different vessel types and provide a comprehensive characterization of the arachnoid and pial compartments and their connection to CNS vessels and perivascular pathways...
April 2018: Journal of Cerebral Blood Flow and Metabolism
Peter Jezzard, Michael A Chappell, Thomas W Okell
Arterial spin labeling (ASL) is an MRI technique that was first proposed a quarter of a century ago. It offers the prospect of non-invasive quantitative measurement of cerebral perfusion, making it potentially very useful for research and clinical studies, particularly where multiple longitudinal measurements are required. However, it has suffered from a number of challenges, including a relatively low signal-to-noise ratio, and a confusing number of sequence variants, thus hindering its clinical uptake. Recently, however, there has been a consensus adoption of an accepted acquisition and analysis framework for ASL, and thus a better penetration onto clinical MRI scanners...
April 2018: Journal of Cerebral Blood Flow and Metabolism
Muhammad E Haque, Refaat E Gabr, Xiurong Zhao, Khader M Hasan, Andrew Valenzuela, Ponnada A Narayana, Shun-Ming Ting, Guanghua Sun, Sean I Savitz, Jaroslaw Aronowski
Iron released after intracerebral hemorrhage (ICH) is damaging to the brain. Measurement of the content and distribution of iron in the hematoma could predict brain damage. In this study, 16 Yorkshire piglets were subjected to autologous blood injection ICH model and studied longitudinally using quantitative susceptibility mapping and R2* relaxivity MRI on day 1 and 7 post-ICH. Phantom calibration of susceptibility demonstrated (1) iron distribution heterogeneity within the hematoma and (2) natural absorption of iron from 154 ± 78 µg/mL (day 1) to 127 ± 33 µg/mL (day 7)...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Alois J Schiefecker, Mario Kofler, Max Gaasch, Ronny Beer, Iris Unterberger, Bettina Pfausler, Gregor Broessner, Peter Lackner, Paul Rhomberg, Elke Gizewski, Werner O Hackl, Miriam Mulino, Martin Ortler, Claudius Thome, Erich Schmutzhard, Raimund Helbok
Spreading depolarizations (SDs) are highly active metabolic events, commonly occur in patients with intracerebral hemorrhage (ICH) and may be triggered by fever. We investigated the dynamics of brain-temperature (Tbrain ) and core-temperature (Tcore ) relative to the occurrence of SDs. Twenty consecutive comatose ICH patients with multimodal electrocorticograpy (ECoG) and Tbrain monitoring of the perihematomal area were prospectively enrolled. Clusters of SDs were defined as ≥2 SDs/h. Generalized estimating equations were used for statistical calculations...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Zheng Zachory Wei, James Ya Zhang, Tammi M Taylor, Xiaohuan Gu, Yingying Zhao, Ling Wei
Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Brandon Foreman, David Albers, J Michael Schmidt, Cristina Maria Falo, Angela Velasquez, E Sander Connolly, Jan Claassen
Subarachnoid hemorrhage (SAH) is a devastating form of stroke. Approximately one in four patients develop progressive neurological deterioration and silent infarction referred to as delayed cerebral ischemia (DCI). DCI is a complex, multifactorial secondary brain injury pattern and its pathogenesis is not fully understood. We aimed to study the relationship between cerebral blood flow (CBF) and neuronal activity at both the cortex and in scalp using electroencephalography (EEG) in poor-grade SAH patients undergoing multimodality intracranial neuromonitoring...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Alexandre Bizeau, Guillaume Gilbert, Michaël Bernier, Minh Tung Huynh, Christian Bocti, Maxime Descoteaux, Kevin Whittingstall
The high metabolic demand of neuronal tissue, coupled with its relatively low energy storage capacity, requires that increases in neuronal activation are quickly matched with increased blood flow to ensure efficient supply of oxygen and nutrients to the tissue. For this to occur, dilation of nearby arterioles must be coordinated with the dilation of larger upstream feeding arteries. As it stands, the exact spatial extent of such dilation in humans is unknown. Using non-invasive time-of-flight magnetic resonance angiography in healthy participants, we developed an automatic methodology for reconstructing cerebral arterial vessels and quantifying their diameter on a voxel-by-voxel basis...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Kari A Duck, Elizabeth B Neely, Ian A Simpson, James R Connor
HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood-brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Masato Kobayashi, Teresa Jiang, Sanjay Telu, Sami S Zoghbi, Roger N Gunn, Eugenii A Rabiner, David R Owen, Qi Guo, Victor W Pike, Robert B Innis, Masahiro Fujita
Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent 11 C-( R)-PK11195 in human imaging. This study sought to quantitatively measure the "signal to background" ratio (assessed as binding potential ( BPND )) of 11 C-( R)-PK11195 compared to one of the most promising second-generation radioligands, 11 C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either 11 C-( R)-PK11195 (16 subjects) or 11 C-DPA-713 (22 subjects)...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Mario Kofler, Alois J Schiefecker, Ronny Beer, Maxime Gaasch, Paul Rhomberg, John Stover, Bettina Pfausler, Claudius Thomé, Erich Schmutzhard, Raimund Helbok
Low brain tissue glucose levels after acute brain injury are associated with poor outcome. Whether enteral nutrition (EN) reliably increases cerebral glucose levels remains unclear. In this retrospective analysis of prospectively collected observational data, we investigate the effect of EN on brain metabolism in 17 poor-grade subarachnoid hemorrhage (SAH) patients undergoing cerebral microdialysis (CMD) monitoring. CMD-values were obtained hourly. A nutritional intervention was defined as the clinical routine administration of EN without supplemental parenteral nutrition...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Devin W McBride, Derek Nowrangi, Harpreet Kaur, Guangyong Wu, Lei Huang, Tim Lekic, Jiping Tang, John H Zhang
Cerebellar haemorrhage accounts for 5-10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Jacob K Rasmussen, Ebbe Boedtkjer
The CO2 /HCO3 - buffer minimizes pH changes in response to acid-base loads, HCO3 - provides substrate for Na+ ,HCO3 - -cotransporters and Cl- /HCO3 - -exchangers, and H+ and HCO3 - modify vasomotor responses during acid-base disturbances. We show here that rat middle cerebral arteries express cytosolic, mitochondrial, extracellular, and secreted carbonic anhydrase isoforms that catalyze equilibration of the CO2 /HCO3 - buffer. Switching from CO2 /HCO3 - -free to CO2 /HCO3 - -containing extracellular solution results in initial intracellular acidification due to hydration of CO2 followed by gradual alkalinization due to cellular HCO3 - uptake...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Laiting Chi, Kairong Du, Dongdong Liu, Yulong Bo, Wenzhi Li
The demand for using parasympathetic activation for stroke therapy is unmet. In the current study, we investigated whether the neuroprotection provided by electroacupuncture (EA) in an experimental stroke model was associated with activation of the parasympathetic nervous system (PNS). The results showed that parasympathetic dysfunction (PD), performed as unilateral vagotomy combined with peripheral atropine, attenuated both the functional benefits of EA and its effects in improving cerebral perfusion, reducing infarct volume, and hindering apoptosis, neuronal and peripheral inflammation, and oxidative stress...
March 2018: Journal of Cerebral Blood Flow and Metabolism
Maria Angela Guzzardi, Elena Sanguinetti, Antonietta Bartoli, Alessandra Kemeny, Daniele Panetta, Piero A Salvadori, Silvia Burchielli, Patricia Iozzo
Obesity and diabetes associate with neurodegeneration. Brain glucose and BDNF are fundamental in perinatal development. BDNF is related to brain health, food intake and glucose metabolism. We characterized the relationship between glycemia and/or brain glucose utilization (by 18 FDG-PET during fasting and glucose loading), obesity and BDNF in 4-weeks old (pre-obese) and 12-weeks old (obese) Zucker fa/fa rats, and their age-matched fa/+ controls. In 75 human infants, we assessed cord blood BDNF and glucose levels, appetite regulating hormones, body weight and maternal factors...
March 2018: Journal of Cerebral Blood Flow and Metabolism
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