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Cx3cr1 stroke

Yifang Fan, Xiaoxing Xiong, Yongming Zhang, Dongmei Yan, Zhihong Jian, Baohui Xu, Heng Zhao
BACKGROUND: MKEY, a synthetic cyclic peptide inhibitor of CXCL4-CCL5 heterodimer formation, has been shown to protect against atherosclerosis and aortic aneurysm formation by mediating inflammation, but whether it modulates neuroinflammation and brain injury has not been studied. We therefore studied the role of MKEY in stroke-induced brain injury in mice. METHODS AND RESULTS: MKEY was injected into mice after stroke with 60 minutes of middle cerebral artery occlusion...
September 2016: Journal of the American Heart Association
Daojing Li, Chunjiong Wang, Yang Yao, Li Chen, Guiyou Liu, Rongxin Zhang, Qiang Liu, Fu-Dong Shi, Junwei Hao
Inflammatory factors secreted by microglia play an important role in focal ischemic stroke. The mammalian target of rapamycin (mTOR) pathway is a known regulator of immune responses, but the role that mTORC1 signaling plays in poststroke neuroinflammation is not clear. To explore the relationship between microglial action in the mTORC1 pathway and the impact on stroke, we administered the mTORC1 inhibitors sirolimus and everolimus to mice. Presumably, disrupting the mTORC1 pathway after focal ischemic stroke should clarify the subsequent activity of microglia...
June 24, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Rodney M Ritzel, Sarah J Pan, Rajkumar Verma, John Wizeman, Joshua Crapser, Anita R Patel, Richard Lieberman, Royce Mohan, Louise D McCullough
PURPOSE: The transient middle cerebral artery occlusion (MCAO) model of stroke is one of the most commonly used models to study focal cerebral ischemia. This procedure also results in the simultaneous occlusion of the ophthalmic artery that supplies the retina. Retinal cell death is seen days after reperfusion and leads to functional deficits; however, the mechanism responsible for this injury has not been investigated. Given that the eye may have a unique ocular immune response to an ischemic challenge, this study examined the inflammatory response to retinal ischemia in the MCAO model...
2016: Molecular Vision
Hyunjung Min, Yong Ho Jang, Ik-Hyun Cho, Seong-Woon Yu, Sung Joong Lee
BACKGROUND: Intracerebral hemorrhage (ICH) is one of the major causes of stroke. After onset of ICH, massive infiltration of macrophages is detected in the peri-hematoma regions. Still, the function of these macrophages in ICH has not been completely elucidated. RESULTS: In a collagenase-induced ICH model, CX3CR1(+) macrophages accumulated in the peri-hematoma region. Characterization of these macrophages revealed expression of alternatively activated (M2) macrophage markers...
2016: Molecular Brain
Liang Wang, Shuai Kang, Dingquan Zou, Lei Zhan, Zhengxi Li, Wan Zhu, Hua Su
Ischemic stroke is a devastating complication of bone fracture. Bone fracture shortly after stroke enhances stroke injury by augmenting inflammation. We hypothesize that bone fracture shortly before ischemic stroke also exacerbates ischemic cerebral injury. Tibia fracture was performed 6 or 24 hours before permanent middle cerebral artery occlusion (pMCAO) on C57BL/6J mice or Ccr2RFP/+Cx3cr1GFP/+ mice that have the RFP gene knocked into one allele of Ccr2 gene and GFP gene knocked into one allele of Cx3cr1 gene...
2016: PloS One
David Fernández-López, Joel Faustino, Alexander L Klibanov, Nikita Derugin, Elodie Blanchard, Franziska Simon, Stephen L Leib, Zinaida S Vexler
Perinatal stroke leads to significant morbidity and long-term neurological and cognitive deficits. The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. To understand whether microglial cells limit injury after neonatal stroke by preserving neurovascular integrity, we subjected postnatal day 7 (P7) rats depleted of microglial cells, rats with inhibited microglial TGFbr2/ALK5 signaling, and corresponding controls, to transient middle cerebral artery occlusion (tMCAO)...
March 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yanina R Timasheva, Timur R Nasibullin, Olga E Mustafina
Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH). The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects)...
September 2015: Cerebrovascular Diseases Extra
Michael Gliem, Markus Schwaninger, Sebastian Jander
Hematogenous recruitment of monocytes and macrophages has traditionally been viewed as a harmful process causing exacerbation of brain injury after stroke. However, emerging findings suggest equally important protective features. Inflammatory monocytes are rapidly recruited to ischemic brain via a CCR2-dependent pathway and undergo secondary differentiation in the target tissue towards non-inflammatory macrophages, mediating neuroprotection and repair of the ischemic neurovascular unit. In contrast, independent recruitment of non-inflammatory monocytes via CX3CR1 does not occur...
March 2016: Biochimica et Biophysica Acta
Helene L Walter, Gerlinde van der Maten, Ana Rita Antunes, Tadeusz Wieloch, Karsten Ruscher
BACKGROUND: Recovery of lost neurological function after stroke is limited and dependent on multiple mechanisms including inflammatory processes. Selective pharmacological modulation of inflammation might be a promising approach to improve stroke outcome. METHODS: We used 1,1'-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and potential allosteric agonist to CXCR7, administered to mice twice daily from day 2 after induction of photothrombosis (PT)...
2015: Journal of Neuroinflammation
Helene L Walter, Gerlinde van der Maten, Ana Rita Antunes, Tadeusz Wieloch, Karsten Ruscher
BACKGROUND: Recovery of lost neurological function after stroke is limited and dependent on multiple mechanisms including inflammatory processes. Selective pharmacological modulation of inflammation might be a promising approach to improve stroke outcome. METHODS: We used 1,1'-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] (AMD3100), an antagonist to the C-X-C chemokine receptor type 4 (CXCR4) and potential allosteric agonist to CXCR7, administered to mice twice daily from day 2 after induction of photothrombosis (PT)...
December 2015: Journal of Neuroinflammation
Oana Herlea-Pana, Longbiao Yao, Janet Heuser-Baker, Qiongxin Wang, Qilong Wang, Constantin Georgescu, Ming-Hui Zou, Jana Barlic-Dicen
AIMS: Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model, we have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial progenitor cell (EPC) treatment...
May 1, 2015: Cardiovascular Research
Valérie Jolivel, Frank Bicker, Fabien Binamé, Robert Ploen, Stefanie Keller, René Gollan, Betty Jurek, Jérôme Birkenstock, Laura Poisa-Beiro, Julia Bruttger, Verena Opitz, Serge C Thal, Ari Waisman, Tobias Bäuerle, Michael K Schäfer, Frauke Zipp, Mirko H H Schmidt
The contribution of microglia to ischemic cortical stroke is of particular therapeutic interest because of the impact on the survival of brain tissue in the ischemic penumbra, a region that is potentially salvable upon a brain infarct. Whether or not tissue in the penumbra survives critically depends on blood flow and vessel perfusion. To study the role of microglia in cortical stroke and blood vessel stability, CX3CR1(+/GFP) mice were subjected to transient middle cerebral artery occlusion and then microglia were investigated using time-lapse two-photon microscopy in vivo...
February 2015: Acta Neuropathologica
Roslyn A Taylor, Matthew D Hammond, Youxi Ai, Lauren H Sansing
Intracerebral hemorrhage is a subset of stroke for which there is no specific treatment. The Ly6Chi CCR2+ monocytes have been shown to contribute to acute injury after intracerebral hemorrhage. The other murine monocyte subset expresses CX3CR1 and lower Ly6C levels, and contributes to repair in other disease models. We hypothesized that the Ly6Clo CX3CR1+ monocytes would contribute to recovery after intracerebral hemorrhage. Intracerebral hemorrhage was modeled by blood injection in WT and CX3CR1-null bone marrow chimeras...
2014: PloS One
Mark Schafer, Holly Kell, James Navalta, Ramires Tibana, Scott Lyons, Scott Arnett
UNLABELLED: Tennis is an activity requiring both endurance and anaerobic components, which could have immunosuppressive effects postexercise. PURPOSE: The purpose of this investigation was to determine the effect of a simulated tennis match on apoptotic and migratory markers on lymphocyte subsets. METHOD: Male high school (n = 5) and college (n = 3) tennis players (M(age) = 18.9 +/- 3.3 years) completed 10 sets of a tennis protocol including serves, forehand strokes, and backhand groundstrokes with 1-min rest periods between sets...
March 2014: Research Quarterly for Exercise and Sport
Paolo Gelosa, Davide Lecca, Marta Fumagalli, Dorota Wypych, Alice Pignieri, Mauro Cimino, Claudia Verderio, Malin Enerbäck, Elham Nikookhesal, Elena Tremoli, Maria P Abbracchio, Luigi Sironi
The ADP-responsive P2Y12 receptor is expressed on both platelets and microglia. Clinical data show that ticagrelor, a direct-acting, reversibly binding P2Y12-receptor antagonist, reduces total cardiovascular events, including stroke. In our present study, we investigated the expression of P2Y12 receptors and the effects of ticagrelor on brain injury in Sprague-Dawley rats subjected to a permanent middle cerebral artery occlusion (MCAo). Rats were treated per os with ticagrelor 3 mg/kg or vehicle at 10 minutes, 22, and 36 hours after MCAo and killed after 48 hours...
June 2014: Journal of Cerebral Blood Flow and Metabolism
Zhiwei Tang, Yan Gan, Qiang Liu, Jun-Xiang Yin, Qingwei Liu, Jiong Shi, Fu-Dong Shi
BACKGROUND: Chemokine (C-X3-C motif) ligand 1 (CX3CL1)/ CX3C chemokine receptor 1 (CX3CR1) signaling is important in modulating the communication between neurons and resident microglia/migrated macrophages in the central nervous system (CNS). Although CX3CR1 deficiency is associated with an improved outcome following ischemic brain injury, the mechanism of this observation is largely unknown. The aim of this study was to investigate how CX3CR1 deficiency influences microglia/macrophage functions in the context of its protection following brain ischemia...
2014: Journal of Neuroinflammation
Jianfeng Ge, Ling Guo, Shan Wang, Yiling Zhang, Ting Cai, Robert C H Zhao, Yaojiong Wu
BACKGROUND AND PURPOSE: Intravascular injection of mesenchymal stem cells (MSCs) has been found to cause considerable vascular obstructions which may lead to serious outcomes, particularly after intra-arterial injection. However, the underlying mechanisms have been poorly understood. METHODS: In this study, we fractionated MSCs that had been cultured in monolayer for six passages into small (average diameter = 17.9 μm) and large (average diameter 30.4 μm) populations according to their sizes, and examined their vascular obstructions after intra-internal carotid artery injection in rats and mice in comparison with MSCs derived from 3D spheroids which were uniformly smaller in size (average diameter 12...
April 2014: Stem Cell Reviews
Ting Li, Shengru Pang, Yongping Yu, Xiaoqian Wu, Jing Guo, Shengxiang Zhang
Stroke induces rapid activation and expansion of microglia, but the main source of microgliosis is controversial. Here we investigated the formation of microgliosis and infiltration of circulating cells in a photothrombosis stroke model by taking advantage of parabiosis and two-photon microscopy. We found that a small population of blood-derived CX3CR1(GFP/+) cells infiltrated the cerebral parenchyma, but these cells did not proliferate and were phenotypically distinguishable from resident microglia. CX3CR1(GFP/+) infiltrating cells also displayed different kinetics from reactive microglia...
December 2013: Brain: a Journal of Neurology
Joseph C Biedenkapp, Lisa R Leon
Heat stroke (HS) is characterized by a systemic inflammatory response syndrome (SIRS) consisting of profound core temperature (Tc) changes in mice. Encephalopathy is common at HS collapse, but inflammatory changes occurring in the brain during the SIRS remain unidentified. We determined the association between inflammatory gene expression changes in the brain with Tc disturbances during HS recovery in mice. Gene expression changes of heat shock protein (HSP)72, heme oxygenase (hmox1), cytokines (IL-1β, IL-6, TNF-α), cyclooxygenase enzymes (COX-1, COX-2), chemokines (MCP-1, MIP-1α, MIP-1β, CX3CR1), and glia activation markers (CD14, aif1, vimentin) were examined in the hypothalamus (HY) and hippocampus (HC) of control (Tc ∼ 36...
November 2013: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Ukpong B Eyo, Sam A Miner, Katelin E Ahlers, Long-Jun Wu, Michael E Dailey
Brain-resident microglia may promote tissue repair following stroke but, like other cells, they are vulnerable to ischemia. Here we identify mechanisms involved in microglial ischemic vulnerability. Using time-lapse imaging of cultured BV2 microglia, we show that simulated ischemia (oxygen-glucose deprivation; OGD) induces BV2 microglial cell death. Removal of extracellular Ca(2+) or application of Brilliant Blue G (BBG), a potent P2X7 receptor (P2X7R) antagonist, protected BV2 microglia from death. To validate and extend these in vitro findings, we assessed parenchymal microglia in freshly isolated hippocampal tissue slices from GFP-reporter mice (CX3CR1(GFP/+))...
October 2013: Neuropharmacology
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