Brain arteriovenous malformations (AVMs) are a disorder wherein abnormal, enlarged blood vessels connect arteries directly to veins, without an intervening capillary bed. AVMs are one of the leading causes of hemorrhagic stroke in children and young adults. Most human sporadic brain AVMs are associated with genetic activating mutations in the KRAS gene. Our goal was to develop an in vitro model that would allow for simultaneous morphological and functional phenotypic data capture in real time during AVM disease progression. By generating human endothelial cells harboring a clinically relevant mutation found in most human patients (activating mutations within the small GTPase KRAS) and seeding them in a dynamic microfluidic cell culture system that enables vessel formation and perfusion, we demonstrate that vessels formed by KRAS4A mutant endothelial cells (ECs) were significantly wider and more leaky than vascular beds formed by wild-type ECs, recapitulating key structural and functional hallmarks of human AVM pathogenesis. Immunofluorescence staining revealed a breakdown of adherens junctions in mutant KRAS vessels, leading to increased vascular permeability, a hallmark of hemorrhagic stroke. Finally, pharmacological blockade of MEK kinase activity, but not PI3K inhibition, improved endothelial barrier function (decreased permeability) without affecting vessel diameter. Collectively, our studies describe the creation of human KRAS-dependent AVM-like vessels in vitro in a self-assembling microvessel platform that is amenable to phenotypic observation and drug delivery.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121729 | DOI Listing |
J Integr Med
December 2024
Yueyang Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Research Institute of Acupuncture and Meridian, Shanghai 200030, China. Electronic address:
Background: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy.
Objective: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach.
J Ethnopharmacol
December 2024
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address:
Ethnopharmacological Relevance: Delayed tissue-type plasminogen activator (t-PA) thrombolysis, which has a restrictive therapeutic time window within 4.5 h following ischemic stroke (IS), increases the risk of hemorrhagic transformation (HT) and subsequent neurotoxicity. Studies have shown that the NLRP3 inflammasome activation reversely regulated by the PGC-1α leads to microglial polarization and pyroptosis to cause damage to nerve cells and the blood-brain barrier.
View Article and Find Full Text PDFJ Neurol Sci
December 2024
Department of Neurology, University of California, San Francisco, USA.
This study examines the relationship between comorbid seizures and dementia among stroke patients using the 2017 Nationwide Inpatient Sample (NIS), the largest publicly available inpatient healthcare database in the United States. We analyzed data from 128,341 stroke patients, including those with ischemic and hemorrhagic strokes, to determine the prevalence of seizures and dementia, and the association between these conditions. Our findings reveal that 7.
View Article and Find Full Text PDFAm J Hypertens
December 2024
Department of Neurosurgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Background: Systolic blood pressure (BP) is a key factor in the outcomes of patients with acute ischemic stroke (AIS) receiving endovascular thrombectomy (EVT). However, the factors that mediate the association between BP and clinical outcome are unclear.
Methods: Consecutive patients with AIS in the anterior circulation underwent continuous blood pressure monitoring for 24 hours.
BMC Neurol
December 2024
Department of Neurology, Mannheim Center for Translational Neuroscience, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim, 68167, Germany.
Background: Neuroimaging plays a vital role in the diagnosis of intracerebral hemorrhage (ICH) and in identifying the underlying etiology for appropriate therapeutic approach. This study aims to determine the significance and potential advantages of using early magnetic resonance imaging (MRI) as a diagnostic tool for ICH.
Methods: This retrospective study included 359 patients with ICH treated at the Department of Neurology, Mannheim University Hospital between January 2017 and December 2021.
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