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https://www.readbyqxmd.com/read/28526762/exacerbation-of-thromboinflammation-by-hyperglycemia-precipitates-cerebral-infarct-growth-and-hemorrhagic-transformation
#1
Jean-Philippe Desilles, Varouna Syvannarath, Véronique Ollivier, Clément Journé, Sandrine Delbosc, Célina Ducroux, William Boisseau, Liliane Louedec, Lucas Di Meglio, Stéphane Loyau, Martine Jandrot-Perrus, Louis Potier, Jean-Baptiste Michel, Mikael Mazighi, Benoit Ho-Tin-Noé
BACKGROUND AND PURPOSE: Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How hyperglycemia impacts the pathophysiology of acute ischemic stroke remains largely unknown. We investigated how preexisting hyperglycemia increases ischemia/reperfusion cerebral injury. METHODS: Normoglycemic and streptozotocin-treated hyperglycemic rats were subjected to transient middle cerebral artery occlusion. Infarct growth and brain perfusion were assessed by magnetic resonance imaging...
May 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28521701/unexpected-effects-of-acetylcholine-precursors-on-pilocarpine-seizure-induced-neuronal-death
#2
Minwoo Lee, Bo Young Choi, Sang Won Suh
Choline alfoscerate (α-GPC) and Cytidine 5'-diphosphocholine (CDP-Choline) are both acetylcholine precursors and are considered to act as pro-cholinergic nootropic agents. Acetylcholine precursors have also recently found frequent use in the neurology clinic. Stroke and many types of dementia have been shown to respond favorably after treatment with these agents, not only in terms of cognitive dysfunction but also behavioral and psychological symptoms. The primary mechanisms of Acetylcholine precursors are the following: 1) Acetylcholine precursors themselves are used in the biosynthesis of acetylcholine and 2) byproducts like glycerophosphate have protective functions for neuronal phospholipids...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28510599/selective-inhibition-of-brain-endothelial-rho-kinase-2-provides-optimal-protection-of-an-in-vitro-blood-brain-barrier-from-tissue-type-plasminogen-activator-and-plasmin
#3
Be'eri Niego, Natasha Lee, Pia Larsson, T Michael De Silva, Amanda E-Ling Au, Fiona McCutcheon, Robert L Medcalf
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model...
2017: PloS One
https://www.readbyqxmd.com/read/28507312/design-and-evaluation-of-ephrina1-mutants-with-cerebral-protective-effect
#4
Yuanjun Zhu, Yuanqing Gao, Danping Zheng, Mengyang Shui, Kuai Yu, Xiaoyan Liu, Yuan Lin, Li Su, Wenxing Yang, Yinye Wang
The activation of EphA2 receptor by its natural ligand EphrinA1 causes blood brain barrier dysfunction, and inactivation of EphA2 reduces BBB damage in ischemic stroke. Thus, EphA2 targeted antagonists may serve as neuroprotective agents. We engineered four mutants of EphrinA1, EM1, EM2, EM3 and EM4, respectively. The computational analysis showed that these four mutants were capable of interacting with EphA2. Their potential neuroprotective effects were examined in mouse focal ischemia/reperfusion (I/R) model...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28495827/hyperbaric-oxygen-reduces-infarction-volume-and-hemorrhagic-transformation-through-atp-nad-sirt1-pathway-in-hyperglycemic-middle-cerebral-artery-occlusion-rats
#5
Qin Hu, Anatol Manaenko, Hetao Bian, Zongduo Guo, Jun-Long Huang, Zhen-Ni Guo, Peng Yang, Jiping Tang, John H Zhang
BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion...
May 11, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28484963/blood-brain-barrier-protection-as-a-therapeutic-strategy-for-acute-ischemic-stroke
#6
Ali Ehsan Sifat, Bhuvaneshwar Vaidya, Thomas J Abbruscato
The blood-brain barrier (BBB) is a vital component of the neurovascular unit (NVU) containing tight junctional (TJ) proteins and different ion and nutrient transporters which maintain normal brain physiology. BBB disruption is a major pathological hallmark in the course of ischemic stroke which is regulated by the actions of different factors working at different stages of cerebral ischemia including matrix metalloproteinases (MMPs), inflammatory modulators, vesicular trafficking, oxidative pathways, and junctional-cytoskeletal interactions...
May 8, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28481312/carotid-artery-stenting-and-blood-brain-barrier-permeability-in-subjects-with-chronic-carotid-artery-stenosis
#7
Arkadiusz Szarmach, Grzegorz Halena, Mariusz Kaszubowski, Maciej Piskunowicz, Michal Studniarek, Piotr Lass, Edyta Szurowska, Pawel J Winklewski
Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28481164/diffuse-microvascular-dysfunction-and-loss-of-white-matter-integrity-predict-poor-outcomes-in-patients-with-acute-ischemic-stroke
#8
Natalia S Rost, Pedro Cougo, Svetlana Lorenzano, Hua Li, Lisa Cloonan, Mark Jrj Bouts, Arne Lauer, Mark R Etherton, Hasan H Karadeli, Patricia L Musolino, William A Copen, Ken Arai, Eng H Lo, Steve K Feske, Karen L Furie, Ona Wu
We sought to investigate the relationship between blood-brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM)...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28478842/periodontal-disease-as-a-potential-factor-of-migraine-chronification
#9
Pablo Ameijeira, Yago Leira, Juan Blanco, Rogelio Leira
Migraine is a hereditary constitutional base disorder, which is characterized by recurrent episodes of headache pulsatile characteristics associated with photophobia/phonophobia, nausea and/or vomiting. The main complication in migraine is the chronicity of the process, now recognized as a chronic migraine. Although pathogenic mechanisms that may influence the pathophysiology of migraine and its possible chronicity are not fully understood, previous studies have shown in patients with migraine molecular alterations of systemic inflammation, neurogenic inflammation, endothelial dysfunction, innate immunity, dysfunction of matrix proteases and blood-brain barrier...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28473286/characterization-of-a-novel-murine-model-for-spontaneous-hemorrhagic-stroke-using-in-vivo-pet-and-mr-multiparametric-imaging
#10
Salvador Castaneda Vega, Christine Weinl, Carsten Calaminus, Lisa Wang, Maren Harant, Walter Ehrlichmann, Dennis Thiele, Ursula Kohlhofer, Gerald Reischl, Johann-Martin Hempel, Ulrike Ernemann, Leticia Quintanilla Martinez, Alfred Nordheim, Bernd J Pichler
The clinical use of Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) has proven to be a strong diagnostic tool in the field of neurology. The reliability of these methods to confirm clinical diagnoses has guided preclinical research to utilize these techniques for the characterization of animal disease models. Previously, we demonstrated that an endothelial cell-specific ablation of the murine Serum Response Factor (Srf(iECKO)) results in blood brain barrier (BBB) breakdown and hemorrhagic stroke...
May 1, 2017: NeuroImage
https://www.readbyqxmd.com/read/28469523/role-of-transporters-in-central-nervous-system-drug-delivery-and-blood-brain-barrier-protection-relevance-to-treatment-of-stroke
#11
REVIEW
Hrvoje Brzica, Wazir Abdullahi, Kathryn Ibbotson, Patrick T Ronaldson
Ischemic stroke is a leading cause of morbidity and mortality in the United States. The only approved pharmacologic treatment for ischemic stroke is thrombolysis via recombinant tissue plasminogen activator (r-tPA). A short therapeutic window and serious adverse events (ie, hemorrhage, excitotoxicity) greatly limit r-tPA therapy, which indicates an essential need to develop novel stroke treatment paradigms. Transporters expressed at the blood-brain barrier (BBB) provide a significant opportunity to advance stroke therapy via central nervous system delivery of drugs that have neuroprotective properties...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28469478/spatiotemporal-changes-in-p-glycoprotein-levels-in-brain-and-peripheral-tissues-following-ischemic-stroke-in-rats
#12
Kelly M DeMars, Changjun Yang, Kimberly E Hawkins, Austin O McCrea, David M Siwarski, Eduardo Candelario-Jalil
P-glycoprotein (P-gp) is known to transport a diverse array of xenobiotics, including therapeutic drugs. A member of the ATP-binding cassette (ABC) transporter family, P-gp is a protein encoded by the gene Mdr1 in humans and Abcb1 in rodents (represented by 2 isoforms Abcb1a and Abcb1b). Lining the luminal and abluminal membrane of brain capillary endothelial cells, P-gp is a promiscuous efflux pump extruding a variety of exogenous toxins and drugs. In this study, we measured dynamic changes in Abcb1a and Abcb1b transcripts and P-gp protein in the brain, liver, and kidney after experimental stroke...
2017: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/28467996/increased-risk-of-bullous-pemphigoid-after-first-ever-stroke-a-population-based-study
#13
Ai-Ling Shen, Hsiu-Li Lin, Hsiu-Chen Lin, Yuan-Fu Tseng, Chien-Yeh Hsu, Che-Yi Chou
BACKGROUND: We hypothesize that autoantibodies are induced after the blood-brain barrier is damaged by stroke and the risk of bullous pemphigoid (BP) is increased after stroke. We assess the risk of BP after first-ever stroke in a nationwide population-based cohort of first-ever stroke patients. METHODS: We extracted data from the Longitudinal Health Insurance Database 2005 and identified patients with first-ever stroke as well as control patients matched for age, gender, and year of enrollment...
May 4, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28466272/bfgf-protects-against-oxygen-glucose-deprivation-reoxygenation-induced-endothelial-monolayer-permeability-via-s1pr1-dependent-mechanisms
#14
Li Lin, Qingzhi Wang, Kenny Qian, Zeyuan Cao, Jian Xiao, Xiaoying Wang, Xiaokun Li, Zhanyang Yu
Blood-brain barrier (BBB) disruption is a common pathological feature of many neurological disorders including stroke and brain trauma, therefore is an important therapeutic target for treatment of these diseases. Basic fibroblast growth factor (bFGF) as a member of FGF superfamily plays critical roles in angiogenesis, neurogenesis, and neuron survival. We recently showed that recombinant bFGF protects against BBB disruption in traumatic brain injury in mice. In this study, we further investigated the mechanisms of recombinant bFGF in BBB protection by measuring the permeability of cultured endothelial cell monolayer induced by oxygen-glucose deprivation and reoxygenation (OGD/R)...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28456933/genetic-deletion-of-kr%C3%A3-ppel-like-factor-11-aggravates-ischemic-brain-injury
#15
Xuelian Tang, Kai Liu, Milton H Hamblin, Yun Xu, Ke-Jie Yin
Krüppel-like factors (KLFs) belong to the zinc finger family of transcription factors, and their function in the CNS is largely unexplored. KLF11 is a member of the KLF family, and we have previously demonstrated that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs recruitment of KLF11 as its critical coactivator. Here, we sought to determine the role of KLF11 itself in cerebrovascular function and the pathogenesis of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) was performed in KLF11 knockout and wild-type control mice, and brain infarction was analyzed by TTC staining...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28446746/peripheral-blood-akap7-expression-as-an-early-marker-for-lymphocyte-mediated-post-stroke-blood-brain-barrier-disruption
#16
Grant C O'Connell, Madison B Treadway, Ashley B Petrone, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446207/memory-is-preserved-in-older-adults-taking-at1-receptor-blockers
#17
Jean K Ho, Daniel A Nation
BACKGROUND: Prior work suggests that some but not all antihypertensive treatments may benefit cognition and risk for Alzheimer's disease, independent of stroke. Angiotensin II receptor blockers (ARBs) have been highlighted as one antihypertensive drug class that may confer greatest benefit. METHODS: The participants comprised 1626 nondemented adults, aged 55-91 years, recruited from Alzheimer's Disease Neuroimaging Initiative sites. Three groups were compared: ARB users (HTN-ARBs), other antihypertensive drug users (HTN-Other), and normotensives...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28445478/delayed-histochemical-alterations-within-the-neurovascular-unit-due-to-transient-focal-cerebral-ischemia-and-experimental-treatment-with-neurotrophic-factors
#18
Dominik Michalski, Roman Pitsch, Deepu R Pillai, Bianca Mages, Susanne Aleithe, Jens Grosche, Henrik Martens, Felix Schlachetzki, Wolfgang Härtig
Current stroke therapy is focused on recanalizing strategies, but neuroprotective co-treatments are still lacking. Modern concepts of the ischemia-affected neurovascular unit (NVU) and surrounding penumbra emphasize the complexity during the transition from initial damaging to regenerative processes. While early treatment with neurotrophic factors was shown to result in lesion size reduction and blood-brain barrier (BBB) stabilization, cellular consequences from these treatments are poorly understood. This study explored delayed cellular responses not only to ischemic stroke, but also to an early treatment with neurotrophic factors...
2017: PloS One
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#19
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28439518/diabetes-adult-neurogenesis-and-brain-remodeling-new-insights-from-rodent-and-zebrafish-models
#20
REVIEW
Anne-Claire Dorsemans, David Couret, Anaïs Hoarau, Olivier Meilhac, Christian Lefebvre d'Hellencourt, Nicolas Diotel
The prevalence of diabetes rapidly increased during the last decades in association with important changes in lifestyle. Diabetes and hyperglycemia are well-known for inducing deleterious effects on physiologic processes, increasing for instance cardiovascular diseases, nephropathy, retinopathy and foot ulceration. Interestingly, diabetes also impairs brain morphology and functions such as (1) decreased neurogenesis (proliferation, differentiation and cell survival), (2) decreased brain volumes, (3) increased blood-brain barrier leakage, (4) increased cognitive impairments, as well as (5) increased stroke incidence and worse neurologic outcomes following stroke...
2017: Neurogenesis (Austin, Tex.)
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