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Journal of Cerebral Blood Flow and Metabolism

Karishma Chhabria, Karen Plant, Oliver Bandmann, Robert N Wilkinson, Chris Martin, Elisabeth Kugler, Paul A Armitage, Paola Lm Santoscoy, Vincent T Cunliffe, Jan Huisken, Alexander McGown, Tennore Ramesh, Tim Ja Chico, Clare Howarth
Neurovascular coupling (through which local cerebral blood flow changes in response to neural activation are mediated) is impaired in many diseases including diabetes. Current preclinical rodent models of neurovascular coupling rely on invasive surgery and instrumentation, but transgenic zebrafish coupled with advances in imaging techniques allow non-invasive quantification of cerebrovascular anatomy, neural activation, and cerebral vessel haemodynamics. We therefore established a novel non-invasive, non-anaesthetised zebrafish larval model of neurovascular coupling, in which visual stimulus evokes neuronal activation in the optic tectum that is associated with a specific increase in red blood cell speed in tectal blood vessels...
November 6, 2018: Journal of Cerebral Blood Flow and Metabolism
Cesar V Borlongan, Hung Nguyen, Trenton Lippert, Eleonora Russo, Julian Tuazon, Kaya Xu, Jea-Young Lee, Paul R Sanberg, Yuji Kaneko, Eleonora Napoli
Stroke is a major cause of death and disability in the United States and around the world with limited therapeutic option. Here, we discuss the critical role of mitochondria in stem cell-mediated rescue of stroke brain by highlighting the concept that deleting the mitochondria from stem cells abolishes the cells' regenerative potency. The application of innovative approaches entailing generation of mitochondria-voided stem cells as well as pharmacological inhibition of mitochondrial function may elucidate the mechanism underlying transfer of healthy mitochondria to ischemic cells, thereby providing key insights in the pathology and treatment of stroke and other brain disorders plagued with mitochondrial dysfunctions...
October 30, 2018: Journal of Cerebral Blood Flow and Metabolism
Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe
The ubiquitin-proteasome system (UPS) and autophagy are two major pathways to degrade misfolded proteins that accumulate under pathological conditions. When UPS is overloaded, the degeneration pathway may switch to autophagy to remove excessive misfolded proteins. However, it is still unclear whether and how this switch occurs during cerebral ischemia. In the present study, transient middle cerebral artery occlusion (tMCAO) resulted in accelerated ubiquitin-positive protein aggregation from 0.5 h of reperfusion in mice brain after 10, 30 or 60 min of tMCAO...
October 30, 2018: Journal of Cerebral Blood Flow and Metabolism
Tiffany S Ko, Constantine D Mavroudis, Wesley B Baker, Vincent C Morano, Kobina Mensah-Brown, Timothy W Boorady, Alexander L Schmidt, Jennifer M Lynch, David R Busch, Javier Gentile, George Bratinov, Yuxi Lin, Sejin Jeong, Richard W Melchior, Tami M Rosenthal, Brandon C Shade, Kellie L Schiavo, Rui Xiao, J William Gaynor, Arjun G Yodh, Todd J Kilbaugh, Daniel J Licht
Management of deep hypothermic (DH) cardiopulmonary bypass (CPB), a critical neuroprotective strategy, currently relies on non-invasive temperature to guide cerebral metabolic suppression during complex cardiac surgery in neonates. Considerable inter-subject variability in temperature response and residual metabolism may contribute to the persisting risk for postoperative neurological injury. To characterize and mitigate this variability, we assess the sufficiency of conventional nasopharyngeal temperature (NPT) guidance, and in the process, validate combined non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for direct measurement of cerebral metabolic rate of oxygen ( CMRO2 )...
October 30, 2018: Journal of Cerebral Blood Flow and Metabolism
Pablo Bascuñana, Mirjam Brackhan, Ina Leiter, Heike Keller, Ina Jahreis, Tobias L Ross, Frank M Bengel, Marion Bankstahl, Jens P Bankstahl
Alterations in metabolism during epileptogenesis may be a therapy target. Recently, an increase in amino acid transport into the brain was proposed to play a role in epileptogenesis. We aimed to characterize alterations of substrate utilization during epileptogenesis and in chronic epilepsy. The lithium-pilocarpine post status epilepticus (SE) rat model was used. We performed longitudinal O-(2-[(18)F]fluoroethyl)-l-tyrosine (18 F-FET) and 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) and calculated 18 F-FET volume of distribution (Vt ) and 18 F-FDG uptake...
October 30, 2018: Journal of Cerebral Blood Flow and Metabolism
Milou Straathof, Michel Rt Sinke, Rick M Dijkhuizen, Willem M Otte
The mammalian brain is composed of densely connected and interacting regions, which form structural and functional networks. An improved understanding of the structure-function relation is crucial to understand the structural underpinnings of brain function and brain plasticity after injury. It is currently unclear how functional connectivity strength relates to structural connectivity strength. We obtained an overview of recent papers that report on correspondences between quantitative functional and structural connectivity measures in the mammalian brain...
October 30, 2018: Journal of Cerebral Blood Flow and Metabolism
Anna Andrzejewska, Adam Nowakowski, Tomasz Grygorowicz, Sylwia Dabrowska, Jarosław Orzel, Piotr Walczak, Barbara Lukomska, Miroslaw Janowski
Therapeutic potential of mesenchymal stem cells (MSCs) has been reported consistently in animal models of stroke, with mechanism mainly through immunomodulation and paracrine activity. Intravenous injection has been a prevailing route for MSCs administration, but cell quantities needed when scaling-up from mouse to human are extremely high putting into question feasibility of that approach. Intra-arterial delivery directly routes the cells to the brain thus lowering the required dose. Cell engineering may additionally improve cell homing, further potentiating the value of intra-arterial route...
October 26, 2018: Journal of Cerebral Blood Flow and Metabolism
Camille Blochet, Lara Buscemi, Tifenn Clément, Sabrina Gehri, Jérôme Badaut, Lorenz Hirt
Complex cellular and molecular events occur in the neurovascular unit after stroke, such as blood-brain barrier (BBB) dysfunction and inflammation that contribute to neuronal death, neurological deterioration and mortality. Caveolin-1 (Cav-1) has distinct physiological functions such as caveolae formation associated with endocytosis and transcytosis as well as in signaling pathways. Cav-1 has been proposed to be involved in BBB dysfunction after brain injury; however, its precise role is poorly understood. The goal of this study was to characterize the expression and effect of Cav-1 deletion on outcome in the first week in a transient Middle Cerebral Artery Occlusion stroke model...
October 24, 2018: Journal of Cerebral Blood Flow and Metabolism
Viktoria Zoufal, Thomas Wanek, Markus Krohn, Severin Mairinger, Thomas Filip, Michael Sauberer, Johann Stanek, Thomas Pekar, Martin Bauer, Jens Pahnke, Oliver Langer
P-glycoprotein (P-gp, ABCB1) is an efflux transporter at the blood-brain barrier (BBB), which mediates clearance of beta-amyloid (Aβ) from brain into blood. We used ( R)-[11 C]verapamil PET in combination with partial P-gp inhibition with tariquidar to measure cerebral P-gp function in a beta-amyloidosis mouse model (APPtg) and in control mice at three different ages (50, 200 and 380 days). Following tariquidar pre-treatment (4 mg/kg), whole brain-to-plasma radioactivity concentration ratios ( Kp,brain ) were significantly higher in APPtg than in wild-type mice aged 50 days, pointing to decreased cerebral P-gp function...
October 24, 2018: Journal of Cerebral Blood Flow and Metabolism
Adriano Bernini, Mojgan Masoodi, Daria Solari, John-Paul Miroz, Laurent Carteron, Nicolas Christinat, Paola Morelli, Maurice Beaumont, Samia Abed-Maillard, Mickael Hartweg, Fabien Foltzer, Philippe Eckert, Bernard Cuenoud, Mauro Oddo
Adaptive metabolic response to injury includes the utilization of alternative energy substrates - such as ketone bodies (KB) - to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n = 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and β-hydroxybutyrate). Nutrition - from fasting vs. stable nutrition state - was associated with a significant decrease of brain KB (34...
October 24, 2018: Journal of Cerebral Blood Flow and Metabolism
Jan Willem J Elting, Jeanette Tas, Marcel Jh Aries, Marek Czosnyka, Natasha M Maurits
We analysed mean arterial blood pressure, cerebral blood flow velocity, oxygenated haemoglobin and deoxygenated haemoglobin signals to estimate dynamic cerebral autoregulation. We compared macrovascular (mean arterial blood pressure-cerebral blood flow velocity) and microvascular (oxygenated haemoglobin-deoxygenated haemoglobin) dynamic cerebral autoregulation estimates during three different conditions: rest, mild hypocapnia and hypercapnia. Microvascular dynamic cerebral autoregulation estimates were created by introducing the constant time lag plus constant phase shift model, which enables correction for transit time, blood flow and blood volume oscillations (TT-BF/BV correction)...
October 24, 2018: Journal of Cerebral Blood Flow and Metabolism
Marcelo Rocha, Ashutosh P Jadhav, Tudor G Jovin
No abstract text is available yet for this article.
October 23, 2018: Journal of Cerebral Blood Flow and Metabolism
Linfang Lan, Xinyi Leng, Vincent Ip, Yannie Soo, Jill Abrigo, Haipeng Liu, Florence Fan, Sze Ho Ma, Karen Ma, Bonaventure Ym Ip, Ka Lung Chan, Vincent Ct Mok, David S Liebeskind, Ka Sing Wong, Thomas W Leung
We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography...
October 23, 2018: Journal of Cerebral Blood Flow and Metabolism
Toshimitsu Okamura, Maki Okada, Tatsuya Kikuchi, Hidekatsu Wakizaka, Ming-Rong Zhang
Accumulation of detrimental glutathione-conjugated metabolites in the brain potentially causes neurological disorders, and must therefore be exported from the brain. However, in vivo mechanisms of glutathione-conjugates efflux from the brain remain unknown. We investigated the involvement of transporters in glutathione-conjugates efflux using 6-bromo-7-[11 C]methylpurine ([11 C]1), which enters the brain and is converted into its glutathione conjugate, S-(7-[11 C]methylpurin-6-yl)glutathione ([11 C]2). In mice of control and knockout of P-glycoprotein/breast cancer resistance protein and multidrug resistance-associated protein 2 ([ Mrp2] -/- ), [11 C]2 formed in the brain was rapidly cleared, with no significant difference in efflux rate...
October 22, 2018: Journal of Cerebral Blood Flow and Metabolism
Soren Christensen, Maarten G Lansberg
No abstract text is available yet for this article.
October 22, 2018: Journal of Cerebral Blood Flow and Metabolism
Margaret E Tome, Chelsea K Jarvis, Charles P Schaefer, Leigh M Jacobs, Joseph M Herndon, Kristen C Hunn, Nathan B Arkwright, Kathryn L Kellohen, Peyton C Mierau, Thomas P Davis
P-glycoprotein (PgP) is the major drug efflux pump in human cerebral microvessels. PgP prevents pathogens, toxins and therapeutic drugs from entering the CNS. Understanding the molecular regulation of PgP activity will suggest novel mechanisms to improve CNS drug delivery. Previously, we found that during peripheral inflammatory pain (PIP) (3 h after λ carrageenan injection in the rat paw), PgP traffics to the cortical microvessel endothelial cell plasma membrane concomitant with increased PgP activity. In the current study, we measured the changes in composition of PgP-containing protein complexes after PIP in rat microvessel isolates...
October 22, 2018: Journal of Cerebral Blood Flow and Metabolism
Xi Lan, Xiaoning Han, Xi Liu, Jian Wang
Inflammatory responses occur rapidly after intracerebral hemorrhage and participate in both short-term toxicity and long-term recovery. Microglia/macrophages react to hemorrhagic injury and exhibit dynamic phenotypes and phagocytic capability. Astrocytes secrete cytokines, chemokines, and gliotransmitters that can regulate neuroinflammation. In addition, infiltrating neutrophils and T-lymphocytes modulate immunoreactions, which further cross-talk with microglia/macrophages. Thus, the search for effective immunotherapy to target specific cell type-mediated inflammation might represent a new direction for intracerebral hemorrhage treatment, separate from traditional anti-inflammatory drug discovery...
October 22, 2018: Journal of Cerebral Blood Flow and Metabolism
Yuichiro Fukumoto, Kenji F Tanaka, Bijay Parajuli, Keisuke Shibata, Hideyuki Yoshioka, Kazuya Kanemaru, Christian Gachet, Kazuhiro Ikenaka, Schuichi Koizumi, Hiroyuki Kinouchi
Extracellular ATP, which is released from damaged cells after ischemia, activates P2 receptors. P2Y1 receptors (P2Y1 R) have received considerable attention, especially in astrocytes, because their activation plays a central role in the regulation of neuron-to-glia communication. However, the functions or even existence of P2Y1 R in microglia remain unknown, despite the fact that many microglial P2 receptors are involved in several brain diseases. Herein, we demonstrate the presence and functional capability of microglial P2Y1 R to provide neuroprotective effects following ischemic stress...
October 18, 2018: Journal of Cerebral Blood Flow and Metabolism
Gina Hadley, Daniel J Beard, Yvonne Couch, Ain A Neuhaus, Bryan A Adriaanse, Gabriele C DeLuca, Brad A Sutherland, Alastair M Buchan
The significant morbidity that accompanies stroke makes it one of the world's most devastating neurological disorders. Currently, proven effective therapies have been limited to thrombolysis and thrombectomy. The window for the administration of these therapies is narrow, hampered by the necessity of rapidly imaging patients. A therapy that could extend this window by protecting neurons may improve outcome. Endogenous neuroprotection has been shown to be, in part, due to changes in mTOR signalling pathways and the instigation of productive autophagy...
October 18, 2018: Journal of Cerebral Blood Flow and Metabolism
Inema E Orukari, Joshua S Siegel, Nicole M Warrington, Grant A Baxter, Adam Q Bauer, Joshua S Shimony, Joshua B Rubin, Joseph P Culver
Glioma growth can cause pervasive changes in the functional connectivity (FC) of brain networks, which has been associated with re-organization of brain functions and development of functional deficits in patients. Mechanisms underlying functional re-organization in brain networks are not understood and efforts to utilize functional imaging for surgical planning, or as a biomarker of functional outcomes are confounded by the heterogeneity in available human data. Here we apply multiple imaging modalities in a well-controlled murine model of glioma with extensive validation using human data to explore mechanisms of FC disruption due to glioma growth...
October 18, 2018: Journal of Cerebral Blood Flow and Metabolism
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