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CO2 cerebrovascular reactivity measured with CBF-MRI in older individuals: Association with cognition, physical function, amyloid, and tau proteins J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-15 Sandeepa Sur, Zixuan Lin, Yang Li, Sevil Yasar, Paul B Rosenberg, Abhay Moghekar, Xirui Hou, Dengrong Jiang, Rita R Kalyani, Kaisha Hazel, George Pottanat, Cuimei Xu, Jay J Pillai, Peiying Liu, Marilyn Albert, Hanzhang Lu
Vascular pathology is the second leading cause of cognitive impairment and represents a major contributing factor in mixed dementia. However, biomarkers for vascular cognitive impairment and dementia (VCID) are under-developed. Here we aimed to investigate the potential role of CO2 Cerebrovascular Reactivity (CVR) measured with phase-contrast quantitative flow MRI in cognitive impairment and dementia
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Metabolic coupling between glutamate and N-acetylaspartate in the human brain J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-14 Sungtak Hong, Jyoti Singh Tomar, Jun Shen
A metabolic coupling between glutamate and N-acetylaspartate measured by in vivo magnetic resonance spectroscopy has been recently reported in the literature with inconsistent findings. In this study, confounders originating from Pearson’s spurious correlation of ratios and spectral correlation due to overlapping magnetic resonance spectroscopy signals of glutamate and N-acetylaspartate were practically
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Perfusion imaging by arterial spin labeling in migraine: A literature review J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-14 Severin Schramm, Corinna Börner, Miriam Reichert, Gabriel Hoffmann, Stephan Kaczmarz, Michael Griessmair, Kirsten Jung, Maria T Berndt, Claus Zimmer, Thomas Baum, Florian Heinen, Michaela V Bonfert, Nico Sollmann
Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method for the assessment of cerebral blood flow (CBF). This review summarizes recent ASL-based investigations in adult and pediatric patients with migraine with aura, migraine without aura, and chronic migraine. A systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
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PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-13 Vasily Belov, Nicolas J Guehl, Sridhar Duvvuri, Philip Iredale, Sung-Hyun Moon, Maeva Dhaynaut, Srinivas Chakilam, Alexander C MacDonagh, Peter A Rice, Daniel L Yokell, John J Renger, Georges El Fakhri, Marc D Normandin
Stimulation of the M4 muscarinic acetylcholine receptor reduces striatal hyperdopaminergia, suggesting its potential as a therapeutic target for schizophrenia. Emraclidine (CVL-231) is a novel, highly selective, positive allosteric modulator (PAM) of M4 muscarinic acetylcholine receptors i.e. acts as a modulator that increases the response of these receptors. First, we aimed to further characterize
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Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-13 Akiyo Natsubori, Soojin Kwon, Yoshiko Honda, Takashi Kojima, Akihiro Karashima, Kazuto Masamoto, Makoto Honda
Neurovascular coupling (NVC) is the functional hyperemia of the brain responding to local neuronal activity. It is mediated by astrocytes and affected by subcortical ascending pathways in the cortex that convey information, such as sensory stimuli and the animal condition. Here, we investigate the influence of the raphe serotonergic system, a subcortical ascending arousal system in animals, on the
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Letter to the editor: Deriving transfer function analysis metrics from driven methods J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-11 Joel S Burma, Jonathan D Smirl
Driven and spontaneous methods have been used to quantify the cerebral pressure-flow relationship via transfer function analysis (TFA). Commonly, TFA derived estimates are assessed using band averages within the very-low (0.02–0.07 Hz) and low (0.07–0.20 Hz) frequency during spontaneous oscillations but are quantified at frequencies of interest where blood pressure oscillations are driven (e.g., 0
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The effectiveness and safety of human urinary kallidinogenase in acute ischemic stroke patients undergoing endovascular therapy J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-09 Mengmeng Wang, Changwei Guo, Jie Yang, Jing Li, Jinrong Hu, Zhouzhou Peng, Meng Guo, Lingyu Zhang, Fengli Li, Qingwu Yang, Wenjie Zi, Pengfei Wang
The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale
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Vascular contributions to cognitive decline: Beyond amyloid and tau in the Harvard aging brain study J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-07 Zahra Shirzadi, Rory Boyle, Wai-Ying W Yau, Gillian Coughlan, Jessie Fanglu Fu, Michael J Properzi, Rachel F Buckley, Hyun-Sik Yang, Catherine E Scanlon, Stephanie Hsieh, Rebecca E Amariglio, Kathryn Papp, Dorene Rentz, Julie C Price, Keith A Johnson, Reisa A Sperling, Jasmeer P Chhatwal, Aaron P Schultz
In addition to amyloid and tau pathology, elevated systemic vascular risk, white matter injury, and reduced cerebral blood flow contribute to late-life cognitive decline. Given the strong collinearity among these parameters, we proposed a framework to extract the independent latent features underlying cognitive decline using the Harvard Aging Brain Study (N = 166 cognitively unimpaired older adults
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The brain’s “dark energy” puzzle: How strongly is glucose metabolism linked to resting-state brain activity? J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-06 Tommaso Volpi, Erica Silvestri, Marco Aiello, John J Lee, Andrei G Vlassenko, Manu S Goyal, Maurizio Corbetta, Alessandra Bertoldo
Brain glucose metabolism, which can be investigated at the macroscale level with [18F]FDG PET, displays significant regional variability for reasons that remain unclear. Some of the functional drivers behind this heterogeneity may be captured by resting-state functional magnetic resonance imaging (rs-fMRI). However, the full extent to which an fMRI-based description of the brain’s spontaneous activity
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Long-term isoflurane anesthesia induces cognitive deficits via AQP4 depolarization mediated blunted glymphatic inflammatory proteins clearance J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-05 Rui Dong, Yuqiang Han, Pin Lv, Linhao Jiang, Zimo Wang, Liangyu Peng, Shuai Liu, Zhengliang Ma, Tianjiao Xia, Bing Zhang, Xiaoping Gu
Perioperative neurocognitive disorders (PND) refer to cognitive deterioration that occurs after surgery or anesthesia. Prolonged isoflurane exposure has potential neurotoxicity and induces PND, but the mechanism is unclear. The glymphatic system clears harmful metabolic waste from the brain. This study sought to unveil the functions of glymphatic system in PND and explore the underlying molecular mechanisms
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Lower GLUT1 and unchanged MCT1 in Alzheimer’s disease cerebrovasculature J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-05 Manon Leclerc, Cyntia Tremblay, Philippe Bourassa, Julie A Schneider, David A Bennett, Frédéric Calon
The brain is a highly demanding organ, utilizing mainly glucose but also ketone bodies as sources of energy. Glucose transporter-1 (GLUT1) and monocarboxylates transporter-1 (MCT1) respectively transport glucose and ketone bodies across the blood-brain barrier. While reduced glucose uptake by the brain is one of the earliest signs of Alzheimer’s disease (AD), no change in the uptake of ketone bodies
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Imaging quantitative changes in blood-brain barrier permeability using [18F]2-fluoro-2-deoxy-sorbitol ([18F]FDS) PET in relation to glial cell recruitment in a mouse model of endotoxemia J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-05 Sarah Leterrier, Sébastien Goutal, Gaëlle Hugon, Maud Goislard, Wadad Saba, Benoit Hosten, Simon Specklin, Alexandra Winkeler, Nicolas Tournier
The quantitative relationship between the disruption of the blood-brain barrier (BBB) and the recruitment of glial cells was explored in a mouse model of endotoxemia. [18F]2-Fluoro-2-deoxy-sorbitol ([18F]FDS) PET imaging was used as a paracellular marker for quantitative monitoring of BBB permeability after i.v injection of increasing doses of lipopolysaccharide (LPS) or vehicle (saline, n = 5). The
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Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-04 Clara Correa-Paz, María Pérez-Mato, Mathys Bellemain-Sagnard, Marco González-Domínguez, Pauline Marie, Lara Pérez-Gayol, Esteban López-Arias, Lucia del Pozo-Filíu, Sonia López-Amoedo, Ana Bugallo-Casal, María Luz Alonso-Alonso, María Candamo-Lourido, María Santamaría-Cadavid, Susana Arias-Rivas, Manuel Rodríguez-Yañez, Ramón Iglesias-Rey, José Castillo, Denis Vivien, Marina Rubio, Francisco Campos
Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities
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Comparison of cerebral oxygen extraction fraction using ASE and TRUST methods in patients with sickle cell disease and healthy controls J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-03-04 Slim Fellah, Chunwei Ying, Yan Wang, Kristin P Guilliams, Melanie E Fields, Yasheng Chen, Josiah Lewis, Amy Mirro, Rachel Cohen, Nkemdilim Igwe, Cihat Eldeniz, Dengrong Jiang, Hanzhang Lu, William J Powers, Jin-Moo Lee, Andria L Ford, Hongyu An
Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a
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Pathogenic soluble tau peptide disrupts endothelial calcium signaling and vasodilation in the brain microvasculature J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-29 Amreen Mughal, Adrian M Sackheim, Masayo Koide, Grace Bonson, Grace Ebner, Grant Hennig, Warren Lockette, Mark T Nelson, Kalev Freeman
The accumulation of the microtubule-associated tau protein in and around blood vessels contributes to brain microvascular dysfunction through mechanisms that are incompletely understood. Delivery of nutrients to active neurons in the brain relies on capillary calcium (Ca2+) signals to direct blood flow. The initiation and amplification of endothelial cell Ca2+ signals require an intact microtubule
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No-reflow after recanalization in ischemic stroke: From pathomechanisms to therapeutic strategies J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-29 Feiyue Sun, Jing Zhou, Xiangyu Chen, Tong Yang, Guozuo Wang, Jinwen Ge, Zhanwei Zhang, Zhigang Mei
Endovascular reperfusion therapy is the primary strategy for acute ischemic stroke. No-reflow is a common phenomenon, which is defined as the failure of microcirculatory reperfusion despite clot removal by thrombolysis or mechanical embolization. It has been reported that up to 25% of ischemic strokes suffer from no-reflow, which strongly contributes to an increased risk of poor clinical outcomes.
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Role of microglia after subarachnoid hemorrhage J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-28 David C Lauzier, Umeshkumar Athiraman
Subarachnoid hemorrhage is a devastating sequela of aneurysm rupture. Because it disproportionately affects younger patients, the population impact of hemorrhagic stroke from subarachnoid hemorrhage is substantial. Secondary brain injury is a significant contributor to morbidity after subarachnoid hemorrhage. Initial hemorrhage causes intracranial pressure elevations, disrupted cerebral perfusion pressure
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Sporadic cerebral small vessel disease and cognitive decline in healthy older adults: A systematic review and meta-analysis J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-28 Alexander Jansma, Jeroen de Bresser, Jan W Schoones, Diana van Heemst, Abimbola A Akintola
We performed a systematic review and meta-analysis on prospective studies that provided risk estimates for the impact of 3 different MRI markers of small vessel disease (SVD), namely white matter hyperintensities (WMH), cerebral microbleeds (CMB) and lacunes, on cognitive decline in relatively healthy older adults without cognitive deficits at baseline. A total of 23 prospective studies comprising
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Commentary to “Lower middle cerebral artery blood velocity during low-volume high-intensity interval exercise in chronic stroke” J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-28 Andrew D Robertson
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CNS resident macrophages enhance dysfunctional angiogenesis and circulating monocytes infiltration in brain arteriovenous malformation J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-28 Li Ma, Xiaonan Zhu, Chaoliang Tang, Peipei Pan, Alka Yadav, Rich Liang, Kelly Press, Jeffrey Nelson, Hua Su
Myeloid immune cells are abundant in both ruptured and unruptured brain arteriovenous malformations (bAVMs). The role of central nervous system (CNS) resident and circulating monocyte-derived macrophages in bAVM pathogenesis has not been fully understood. We hypothesize that CNS resident macrophages enhance bAVM development and hemorrhage. RNA sequencing using cultured endothelial cells (ECs) and mouse
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Dysmaturation of sleep state and electroencephalographic activity after hypoxia-ischaemia in preterm fetal sheep J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-28 Christopher A Lear, Benjamin A Lear, Joanne O Davidson, Victoria J King, Yoshiki Maeda, Alice McDouall, Simerdeep K Dhillon, Alistair J Gunn, Laura Bennet
Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion
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Association between occlusion location, net water uptake and ischemic lesion growth in large vessel anterior circulation strokes J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-08 Laurens Winkelmeier, Jeremy J Heit, Gabriel Broocks, Julia Prüter, Christian Heitkamp, Maximilian Schell, Gregory W Albers, Maarten G Lansberg, Max Wintermark, André Kemmling, Christian Paul Stracke, Adrien Guenego, Daniel Paech, Jens Fiehler, Tobias D Faizy
Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large
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Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults – A 4D flow MRI study J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-02-05 Cecilia Björnfot, Anders Eklund, Jenny Larsson, William Hansson, Johan Birnefeld, Anders Garpebring, Sara Qvarlander, Lars-Owe D Koskinen, Jan Malm, Anders Wåhlin
White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements
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Validation of a new 3D quantitative BOLD based cerebral oxygen extraction mapping J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-30 Hyunyeol Lee, Jing Xu, Maria A Fernandez-Seara, Felix W Wehrli
Quantitative BOLD (qBOLD) MRI allows evaluation of oxidative metabolism of the brain based purely on an endogenous contrast mechanism. The method quantifies deoxygenated blood volume (DBV) and hemoglobin oxygen saturation level of venous blood (Yv), yielding oxygen extraction fraction (OEF), and along with a separate measurement of cerebral blood flow, cerebral metabolic rate of oxygen (CMRO2) maps
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A dispensable role of oligodendrocyte-derived laminin-α5 in brain homeostasis and intracerebral hemorrhage J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-19 Minkyung Kang, Abhijit Nirwane, Jingsong Ruan, Aravinthan Adithan, Marsilla Gray, Lingling Xu, Yao Yao
Laminin, a major component of the basal lamina in the CNS, is also expressed in oligodendrocytes (OLs). However, the function of OL-derived laminin remains largely unknown. Here, we performed loss-of-function studies using two OL-specific laminin-α5 conditional knockout mouse lines. Both mutants were grossly normal and displayed intact blood-brain barrier (BBB) integrity. In a mouse model of intracerebral
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Vitamin D deficiency promotes intracranial aneurysm rupture J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-19 Tetsuro Kimura, Redi Rahmani, Takeshi Miyamoto, Yoshinobu Kamio, Daisuke Kudo, Hiroki Sato, Taichi Ikedo, Jacob F Baranoski, Hiroki Uchikawa, Jinglu Ai, Michael T Lawton, Tomoki Hashimoto
Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of
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The role of serum/glucocorticoid-regulated kinase 1 in brain function following cerebral ischemia J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-18 Celeste Yin-Chieh Wu, Yulan Zhang, Li Xu, Zhihai Huang, Peibin Zou, Garrett A Clemons, Chun Li, Cristiane T Citadin, Quanguang Zhang, Reggie Hui-Chao Lee
Cardiopulmonary arrest (CA) is a major cause of death/disability in the U.S. with poor prognosis and survival rates. Current therapeutic challenges are physiologically complex because they involve hypoperfusion (decreased cerebral blood flow), neuroinflammation, and mitochondrial dysfunction. We previously discovered novel serum/glucocorticoid-regulated kinase 1 (SGK1) is highly expressed in brain
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Intraoperative evaluation of local cerebral hemodynamic change by laser speckle contrast imaging for predicting postoperative cerebral hyperperfusion during STA-MCA bypass in adult patients with moyamoya disease J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-18 Tianshu Tao, Wenting Zhu, Jin Yu, Xiang Li, Wei Wei, Miao Hu, Mingrui Luo, Guiping Wan, Pengcheng Li, Jincao Chen, Jianjian Zhang
Cerebral hyperperfusion (CHP) occurred frequently after direct superficial temporal artery–middle cerebral artery (STA-MCA) bypass surgery for moyamoya disease (MMD). We analyzed cortical microvascular density (CMD) and the change of cerebral blood flow (LΔCBF) using intraoperative laser speckle contrast imaging (LSCI) on 130 hemispheres of 95 consecutive adult patients with MMD. The demographic characteristics
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Mesoscopic mapping of hemodynamic responses and neuronal activity during pharmacologically induced interictal spikes in awake and anesthetized mice J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-17 Jing Li, Fan Yang, Fengrui Zhan, Joshua Estin, Aditya Iyer, Mingrui Zhao, James E Niemeyer, Peijuan Luo, Dan Li, Weihong Lin, Jyun-you Liou, Hongtao Ma, Theodore H Schwartz
Imaging hemodynamic responses to interictal spikes holds promise for presurgical epilepsy evaluations. Understanding the hemodynamic response function is crucial for accurate interpretation. Prior interictal neurovascular coupling data primarily come from anesthetized animals, impacting reliability. We simultaneously monitored calcium fluctuations in excitatory neurons, hemodynamics, and local field
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NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-17 Xiao-Yan Lan, Xue-Song Liang, Ming-Xuan Cao, Hua-Min Qin, Cheng-Yan Chu, Johannes Boltze, Shen Li
The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through
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Early remodeling and loss of light-induced dilation of retinal small arteries in CADASIL J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-13 Michel Paques, Valérie Krivosic, Daniela Castro-Farias, Cédric Dulière, Dominique Hervé, Céline Chaumette, Florence Rossant, Abbas Taleb, Jessica Lebenberg, Eric Jouvent, Ramin Tadayoni, Hugues Chabriat
A major hurdle to therapeutic development in cerebral small vessel diseases is the lack of in-vivo method that can be used repeatedly for evaluating directly cerebral microvessels. We hypothesised that Adaptive Optics (AO), which allows resolution images up to 1–2 μm/pixel at retinal level, could provide a biomarker for monitoring vascular changes in CADASIL, a genetic form of such condition. In 98
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Age-related decline in cerebral oxygen consumption in multiple sclerosis J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2024-01-09 Maria H Knudsen, Mark B Vestergaard, Ulrich Lindberg, Helle J Simonsen, Jette L Frederiksen, Stig P Cramer, Henrik BW Larsson
Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry
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Conditioning-based therapeutics for aneurysmal subarachnoid hemorrhage - A critical review. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-28 Sangami Pugazenthi,Aaron J Norris,David C Lauzier,Abhijit V Lele,Anna Huguenard,Rajat Dhar,Gregory J Zipfel,Umeshkumar Athiraman
Aneurysmal subarachnoid hemorrhage (SAH) carries significant mortality and morbidity, with nearly half of SAH survivors having major cognitive dysfunction that impairs their functional status, emotional health, and quality of life. Apart from the initial hemorrhage severity, secondary brain injury due to early brain injury and delayed cerebral ischemia plays a leading role in patient outcome after
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Progressive microvascular failure in acute ischemic stroke: A systematic review, meta-analysis, and time-course analysis. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-28 Thilan Tudor,Eleonora F Spinazzi,Julia E Alexander,Grace K Mandigo,Sean D Lavine,Jack Grinband,E Sander Connolly
This systematic review, meta-analysis, and novel time course analysis examines microvascular failure in the treatment of acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) and/or thrombolytic administration for stroke management. A systematic review and meta-analysis following PRIMSA-2020 guidelines was conducted along with a novel curve-of-best fit analysis to elucidate the
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Astrocyte KDM4A mediates chemokines and drives neutrophil infiltration to aggravate cerebral ischemia and reperfusion injury. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-26 Jing Huang,Xin-Shang Wang,Tian Gao,Xing Wang,Man-Yang Yu,Hao-Xin Song,Bi-Yan Wang,Ling-Mei Li,Qiang Zeng,Hui-Nan Zhang
Neutrophils plays a crucial role in acute ischemic brain injury and have emerged as potential treatment targets to mitigate such injuries. Lysine-specific demethylase 4 A (KDM4A), a member of the histone lysine demethylase family of enzymes involved in transcriptional regulation of gene expression, is upregulated during hypoxic events. However, the exact role of KDM4A in the pathological process of
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Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-24 Ruslan Rust,Mea M Holm,Matteo Egger,Oliver Weinmann,Daniёlle van Rossum,Fruzsina R Walter,Ana Raquel Santa-Maria,Lisa Grönnert,Michael A Maurer,Simon Kraler,Alexander Akhmedov,Rose Cideciyan,Thomas F Lüscher,Maria A Deli,Inge K Herrmann,Martin E Schwab
Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular
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Not open and shut: Complex and prolonged blood-brain barrier responses after stroke. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-24 Emiri T Mandeville,Alastair M Buchan,Steffen Tiedt
Blood-brain barrier dysfunction (BBB) occurs rapidly after stroke and contributes to edema, inflammation, and secondary brain injury including haemorrhage. Two recent studies shed light on the temporal extent of post-stroke BBB dysfunction as well as its consequences for drug delivery. Zhang et al. found increases in BBB permeability that persist up to one-year post-ischemia. Despite increased paracellular
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Peripheral macrophages in the development and progression of structural cerebrovascular pathologies. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-24 David C Lauzier,Anja I Srienc,Ananth K Vellimana,Ralph G Dacey,Gregory J Zipfel
The human cerebrovascular system is responsible for maintaining neural function through oxygenation, nutrient supply, filtration of toxins, and additional specialized tasks. While the cerebrovascular system has resilience imparted by elaborate redundant collateral circulation from supportive tertiary structures, it is not infallible, and is susceptible to developing structural vascular abnormalities
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Proteomic analysis of jugular venous blood in acute large vessel occlusion stroke with futile recanalization. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-24 Xiao-Yan Lan,Di Li,Yu Cui,Thanh N Nguyen,Shen Li,Hui-Sheng Chen
Futile recanalization (FR) after endovascular treatment (EVT) remains a significant challenge for acute ischemic stroke (AIS) with large vessel occlusion (LVO). The pathogenesis of FR has not been well elucidated. We prospectively enrolled anterior circulation LVO-AIS patients who achieved successful recanalization after EVT. The jugular venous blood ipsilateral to stroke was collected before and immediately
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Aberrant vascular architecture in the hippocampus correlates with tau burden in mild cognitive impairment and Alzheimer's disease. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-24 Hansol Lee,Jessie Fanglu Fu,Kyla Gaudet,Annie G Bryant,Julie C Price,Rachel E Bennett,Keith A Johnson,Bradley T Hyman,Trey Hedden,David H Salat,Yi-Fen Yen,Susie Y Huang
Cerebrovascular dysfunction is a significant contributor to Alzheimer's disease (AD) progression. AD mouse models show altered capillary morphology, density, and diminished blood flow in areas of tau and beta-amyloid accumulation. The purpose of this study was to examine alterations in vascular structure and their contributions to perfusion deficits in the hippocampus in AD and mild cognitive impairment
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Neurovascular coupling in early stage dementia - A case-control study. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-22 Suzanne E van Dijk,Nadieh Drenth,Anne Hafkemeijer,Gerda Labadie,Marie-Noëlle W Witjes-Ané,Gerard J Blauw,Serge Arb Rombouts,Jeroen van der Grond,Sanneke van Rooden
Cerebral amyloid angiopathy (CAA) is frequently found post mortem in Alzheimer's dementia, but often undetected during life especially since in vivo hallmarks of CAA and its vascular damage become overt relatively late in the disease process. Decreased neurovascular coupling to visual stimulation has been put forward as an early MRI marker for CAA disease severity. The current study investigates the
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Using digital pathology to analyze the murine cerebrovasculature. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-21 Dana M Niedowicz,Jenna L Gollihue,Erica M Weekman,Panhavuth Phe,Donna M Wilcock,Christopher M Norris,Peter T Nelson
Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges
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Vascular synthesis based on hemodynamic efficiency principle recapitulates measured cerebral circulation properties in the human brain. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-21 Andreas A Linninger,Thomas Ventimiglia,Mohammad Jamshidi,Mathieu Pascal Suisse,Ali Alaraj,Frédéric Lesage,Xin Li,Daniel L Schwartz,William D Rooney
Quantifying anatomical and hemodynamical properties of the brain vasculature in vivo is difficult due to limited spatiotemporal resolution neuroimaging, variability between subjects, and bias between acquisition techniques. This work introduces a metabolically inspired vascular synthesis algorithm for creating a digital representation of the cortical blood supply in humans. Spatial organization and
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Enhanced angiogenesis in the thalamus induced by a novel TSPO ligand ameliorates cognitive deficits after focal cortical infarction. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-21 Yicong Chen,Leo Veenman,Mengshi Liao,Weixian Huang,Jian Yu,Jinsheng Zeng
Neuronal loss in the ipsilateral thalamus after focal cortical infarction participates in post-stroke cognitive deficits, and enhanced angiogenesis in the thalamus is expected to reduce neuronal damage. We hypothesize that novel translocator protein (TSPO) ligand, 2-Cl-MGV-1, can promote angiogenesis, attenuate neuronal loss in the thalamus, and ameliorate post-stroke cognitive deficits. Cortical infarction
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Associations between admission levels of multiple biomarkers and subsequent worse outcomes in acute ischemic stroke patients. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-17 Wei-Li Jia,Ying-Yu Jiang,Yong Jiang,Xia Meng,Hao Li,Xing-Quan Zhao,Yi-Long Wang,Yong-Jun Wang,Hong-Qiu Gu,Zi-Xiao Li
The modified Rankin Scale change score (ΔmRS) is useful for evaluating acute poststroke functional improvement or deterioration. We investigated the relationship between multiple biomarkers and ΔmRS by analyzing data on 6931 patients with acute ischemic stroke (average age 62.3 ± 11.3 years, 2174 (31.4%) female) enrolled from the Third China National Stroke Registry (CNSR-III) and 15 available biomarkers
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Novel voxelwise residual analysis of [11C]raclopride PET data improves detection of low-amplitude dopamine release. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-16 Connor Wj Bevington,Jordan U Hanania,Giovanni Ferraresso,Ju-Chieh Kevin Cheng,Alexandra Pavel,Dongning Su,A Jon Stoessl,Vesna Sossi
Existing methods for voxelwise transient dopamine (DA) release detection rely on explicit kinetic modeling of the [11C]raclopride PET time activity curve, which at the voxel level is typically confounded by noise, leading to poor performance for detection of low-amplitude DA release-induced signals. Here we present a novel data-driven, task-informed method-referred to as Residual Space Detection (RSD)-that
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Diesel exhaust particles exposure exacerbates pro-thrombogenic plasma features ex-vivo after cerebral ischemia and accelerates tPA-induced clot-lysis in hypertensive subjects. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-16 Mercedes Arrúe,Anna Penalba,Ane Rodriguez-Bodero,Amaia Elicegui,Miquel de Homdedeu,María-Jesús Cruz,Alba Simats,Susana Rodriguez,Xavier Buxó,Nicolás Garcia-Rodriguez,Jesús Pizarro,Michelle C Turner,Pilar Delgado,Anna Rosell
The combustion of fossil fuels, mainly by diesel engines, generates Diesel Exhaust Particles (DEP) which are the main source of Particulate Matter (PM), a major air pollutant in urban areas. These particles are a risk factor for stroke with 5.6% of cases attributed to PM exposure. Our aim was to evaluate the effect of DEP exposure on clot formation and lysis in the context of stroke. An ex-vivo clot
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Micro-ultrasound based characterization of cerebrovasculature following focal ischemic stroke and upon short-term rehabilitation. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-16 Johnson Yu,Illsung L Joo,Paolo Bazzigaluppi,Margaret M Koletar,Emmanuel Cherin,Andrew G Stanisz,James Wc Graham,Christine Demore,Bojana Stefanovic
Notwithstanding recanalization treatments in the acute stage of stroke, many survivors suffer long-term impairments. Physical rehabilitation is the only widely available strategy for chronic-stage recovery, but its optimization is hindered by limited understanding of its effects on brain structure and function. Using micro-ultrasound, behavioral testing, and electrophysiology, we investigated the impact
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CCL5 mediated astrocyte-T cell interaction disrupts blood-brain barrier in mice after hemorrhagic stroke. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-16 Shiyi Zhou,Chang Liu,Jixian Wang,Jing Ye,Qianyuan Lian,Lin Gan,Shiyu Deng,Tongtong Xu,Yiyan Guo,Wanlu Li,Zhijun Zhang,Guo-Yuan Yang,Yaohui Tang
The crosstalk between reactive astrocytes and infiltrated immune cells plays a critical role in maintaining blood-brain barrier (BBB) integrity. However, how astrocytes interact with immune cells and the effect of their interaction on BBB integrity after hemorrhagic stroke are still unclear. By performing RNA sequencing in astrocytes that were activated by interleukin-1α (IL-1α), tumor necrosis factor
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Obesity-induced Ly6CHigh and Ly6CLow monocyte subset changes abolish post-ischemic limb conditioning benefits in stroke recovery. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-16 Il-Doo Kim,Hyunwoo Ju,Joseph Minkler,Ahmed Madkoor,Keun Woo Park,Sunghee Cho
Remote limb conditioning (RLC), performed by intermittent interruption of blood flow to a limb, triggers endogenous tolerance mechanisms and improves stroke outcomes. The underlying mechanism for the protective effect involves a shift of circulating monocytes to a Ly6CHigh proinflammatory subset in normal metabolic conditions. The current study investigates the effect of RLC on stroke outcomes in subjects
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Effect of the duration of hypertension on white matter structure and its link with cognition. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-11 Zilin Li,Feng Sang,Zhanjun Zhang,Xin Li
The relation between hypertension (HTN) and cognition has been reported inclusive results, which may be affected by disease duration. Our study aimed to examine the influence of HTN duration on cognition and its underlying white matter (WM) changes including macrostructural WM hyperintensities (WMH) and microstructural WM integrity. A total of 1218 patients aged ≥55 years with neuropsychological assessment
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Estimation of target occupancy in repeated dosing design studies using positron emission tomography: Biases due to target upregulation. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-09 Eugenii A Rabiner,Roger N Gunn
Positron emission tomography (PET) has become indispensable in the quantification of target engagement by brain targeting medications. The relationship between the drug plasma concentration (or drug dose administered) and target occupancy determined during a PET occupancy study has provided valuable information for the assessment of novel pharmaceuticals in the early phases of drug development. Such
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Acute severe hypoglycemia alters mouse brain microvascular proteome. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-09 Siva Svp Sakamuri,Venkata N Sure,Lokanatha Oruganti,William Wisen,Partha K Chandra,Ning Liu,Vivian A Fonseca,Xiaoying Wang,Jennifer Klein,Prasad Vg Katakam
Hypoglycemia increases the risk related to stroke and neurodegenerative diseases, however, the underlying mechanisms are unclear. For the first time, we studied the effect of a single episode (acute) of severe (ASH) and mild (AMH) hypoglycemia on mouse brain microvascular proteome. After four-hour fasting, insulin was administered (i.p) to lower mean blood glucose in mice and induce ∼30 minutes of
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Treatment with the vascular endothelial growth factor-A antibody, bevacizumab, has sex-specific effects in a rat model of mild traumatic brain injury. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-07 Mujun Sun,Tamara L Baker,Campbell T Wilson,Rhys D Brady,Glenn R Yamakawa,David K Wright,Richelle Mychasiuk,Anh Vo,Trevor Wilson,Josh Allen,Stuart J McDonald,Sandy R Shultz
Mild traumatic brain injury (mTBI) involves damage to the cerebrovascular system. Vascular endothelial growth factor-A (VEGF-A) is an important modulator of vascular health and VEGF-A promotes the brain's ability to recover after more severe forms of brain injury; however, the role of VEGF-A in mTBI remains poorly understood. Bevacizumab (BEV) is a monoclonal antibody that binds to VEGF-A and neutralises
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Post-stroke brain can be protected by modulating the lncRNA FosDT. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-07 Suresh L Mehta,Bharath Chelluboina,Kahlilia C Morris-Blanco,Saivenkateshkomal Bathula,Soomin Jeong,Vijay Arruri,Charles K Davis,Raghu Vemuganti
We previously showed that knockdown or deletion of Fos downstream transcript (FosDT; a stroke-induced brain-specific long noncoding RNA) is neuroprotective. We presently tested the therapeutic potential of FosDT siRNA in rodents subjected to transient middle cerebral artery occlusion (MCAO) using the Stroke Treatment Academic Industry Roundtable criteria, including sex, age, species, and comorbidity
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Group 2 innate lymphoid cells suppress neuroinflammation and brain injury following intracerebral hemorrhage. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-11-07 Mingming Liu,Danni Wang,Lin Xu,Yan Pan,Huachen Huang,Minshu Li,Qiang Liu
Intracerebral hemorrhage (ICH) mobilizes circulating leukocytes that contribute to neuroinflammation and neural injury. However, little is known about the endogenous regulatory immune mechanisms to restrict neuroinflammation following ICH. We examined the role of group 2 innate lymphoid cells (ILC2) that are a specialized subset of innate immune modulators in a mouse model of ICH. We found accumulation
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Loss of SARM1 ameliorates secondary thalamic neurodegeneration after cerebral infarction. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-10-28 Kun Zhou,Yan Tan,Guofen Zhang,Jingjing Li,Shihui Xing,Xinran Chen,Jiali Wen,Ge Li,Yuhua Fan,Jinsheng Zeng,Jian Zhang
Ischemic stroke causes secondary neurodegeneration in the thalamus ipsilateral to the infarction site and impedes neurological recovery. Axonal degeneration of thalamocortical fibers and autophagy overactivation are involved in thalamic neurodegeneration after ischemic stroke. However, the molecular mechanisms underlying thalamic neurodegeneration remain unclear. Sterile /Armadillo/Toll-Interleukin
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Cerebral hemodynamics and stroke risks in symptomatic intracranial atherosclerotic stenosis with internal versus cortical borderzone infarcts: A computational fluid dynamics study. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-10-28 Shuang Li,Xuan Tian,Bonaventure Ip,Xueyan Feng,Hing Lung Ip,Jill Abrigo,Linfang Lan,Haipeng Liu,Lina Zheng,Yuying Liu,Yu Liu,Karen Ky Ma,Florence Sy Fan,Sze Ho Ma,Hui Fang,Yuming Xu,Alexander Y Lau,Howan Leung,Yannie Oy Soo,Vincent Ct Mok,Ka Sing Wong,Xinyi Leng,Thomas W Leung
There may be different mechanisms underlying internal (IBZ) and cortical (CBZ) borderzone infarcts in intracranial atherosclerotic stenosis. In 84 patients with symptomatic, 50-99% atherosclerotic stenosis of M1 middle cerebral artery (MCA-M1) with acute borderzone infarcts in diffusion-weighted imaging, we classified the infarct patterns as isolated IBZ (n = 37), isolated CBZ (n = 31), and IBZ+CBZ
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Transnasal cooling: New prospect of selective hypothermia in acute ischemic stroke. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-10-28 Xi Chen,Shuaili Xu,Ming Li,Di Wu,Xunming Ji
Rapid and selective therapeutic hypothermia is a promising neuroprotective method for acute ischemic stroke. A recent study developed a simple but efficient technique of transnasal cooling, in which air at ambient temperature was passed through standard nasal cannula to induce evaporative cooling of the brain. Selective brain temperature decrease was achieved within 25 minutes in piglets. It is a major
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Global, regional, and national burden of ischemic stroke attributed to high low-density lipoprotein cholesterol, 1990-2019:A decomposition analysis and age-period-cohort analysis. J. Cereb. Blood Flow Metab. (IF 6.3) Pub Date : 2023-10-27 Jian Zhang,Shijie Zhu,Chunlong Liu,Yaofeng Hu,Aoran Yang,Yonghui Zhang,Yang Hong
High levels of low-density lipoprotein cholesterol (LDL-C) have been associated with an augmented mortality of ischemic stroke. The yearly deaths and mortality data of IS-hLDL-C were derived from the global burden of disease 2019 dataset. The joinpoint, age-period-cohort and decomposition analysis were utilized to evaluate the long-term patterns in the disease burden of IS-hLDL-C, and the effects of