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CXCR4 Antagonist AMD3100 Protects Blood―Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice
Inflammatory response plays a critical role in propagating tissue damage after focal cerebral ischemia. CXCL12 is a key chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the pharmacological antago...
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| Published in: | Stroke (1970) 2013, Vol.44 (1), p.190-197 |
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| cites | cdi_FETCH-LOGICAL-c500t-50ca818a258c6b9226ee358ee1269bd33189c4556ef61d9b7581f07da548a7c43 |
| container_end_page | 197 |
| container_issue | 1 |
| container_start_page | 190 |
| container_title | Stroke (1970) |
| container_volume | 44 |
| creator | JUN HUANG YANING LI YAOHUI TANG GUANGHUI TANG YANG, Guo-Yuan YONGTING WANG |
| description | Inflammatory response plays a critical role in propagating tissue damage after focal cerebral ischemia. CXCL12 is a key chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the pharmacological antagonist of CXCR4, AMD3100, to investigate the function of CXCL12/CXCR4 in regulating inflammatory response during acute ischemia.
Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain water content, infarct volume, neurological score, and myeloperoxidase (MPO) expression and activity were examined at 24, 48, and 72 hours after MCAO. Proinflammatory cytokine RNA and protein levels in brain tissue were measured by RT-PCR and enzyme linked immunosorbent assay.
Neurological score was greatly improved in AMD3100-treated mice compared with the control mice 3 days after MCAO (P |
| doi_str_mv | 10.1161/strokeaha.112.670299 |
| format | article |
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Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain water content, infarct volume, neurological score, and myeloperoxidase (MPO) expression and activity were examined at 24, 48, and 72 hours after MCAO. Proinflammatory cytokine RNA and protein levels in brain tissue were measured by RT-PCR and enzyme linked immunosorbent assay.
Neurological score was greatly improved in AMD3100-treated mice compared with the control mice 3 days after MCAO (P<0.05). Brain edema-induced change of water content, IgG protein leakage, Evans blue extravasation, occludin, and ZO-1 expression in ipsilateral hemisphere were alleviated by acute treatment of AMD3100. MPO expression and activity revealed that AMD3100 profoundly reduced the number of MPO-positive cells in the ischemic region (P<0.05). It also attenuated proinflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ; their mRNA and protein levels changed accordingly compared with the controls (P<0.05).
CXCR4 antagonist AMD3100 significantly suppressed inflammatory response and reduced blood-brain barrier disruption after MCAO. AMD3100 attenuated ischemia-induced acute inflammation by suppressing leukocyte migration and infiltration, in addition to reducing proinflammatory cytokine expression in the ischemic region.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/strokeaha.112.670299</identifier><identifier>PMID: 23168453</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Biological and medical sciences ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - pathology ; Brain Ischemia - drug therapy ; Brain Ischemia - metabolism ; Brain Ischemia - pathology ; Heterocyclic Compounds - pharmacology ; Heterocyclic Compounds - therapeutic use ; Inflammation - metabolism ; Inflammation - pathology ; Inflammation - prevention & control ; Male ; Medical sciences ; Mice ; Neurology ; Neuropharmacology ; Neuroprotective agent ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Neutrophil Infiltration - drug effects ; Neutrophil Infiltration - physiology ; Pharmacology. Drug treatments ; Receptors, CXCR4 - antagonists & inhibitors ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Stroke (1970), 2013, Vol.44 (1), p.190-197</ispartof><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-50ca818a258c6b9226ee358ee1269bd33189c4556ef61d9b7581f07da548a7c43</citedby><cites>FETCH-LOGICAL-c500t-50ca818a258c6b9226ee358ee1269bd33189c4556ef61d9b7581f07da548a7c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,4031,27935,27936,27937</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27061589$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23168453$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JUN HUANG</creatorcontrib><creatorcontrib>YANING LI</creatorcontrib><creatorcontrib>YAOHUI TANG</creatorcontrib><creatorcontrib>GUANGHUI TANG</creatorcontrib><creatorcontrib>YANG, Guo-Yuan</creatorcontrib><creatorcontrib>YONGTING WANG</creatorcontrib><title>CXCR4 Antagonist AMD3100 Protects Blood―Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>Inflammatory response plays a critical role in propagating tissue damage after focal cerebral ischemia. CXCL12 is a key chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the pharmacological antagonist of CXCR4, AMD3100, to investigate the function of CXCL12/CXCR4 in regulating inflammatory response during acute ischemia.
Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain water content, infarct volume, neurological score, and myeloperoxidase (MPO) expression and activity were examined at 24, 48, and 72 hours after MCAO. Proinflammatory cytokine RNA and protein levels in brain tissue were measured by RT-PCR and enzyme linked immunosorbent assay.
Neurological score was greatly improved in AMD3100-treated mice compared with the control mice 3 days after MCAO (P<0.05). Brain edema-induced change of water content, IgG protein leakage, Evans blue extravasation, occludin, and ZO-1 expression in ipsilateral hemisphere were alleviated by acute treatment of AMD3100. MPO expression and activity revealed that AMD3100 profoundly reduced the number of MPO-positive cells in the ischemic region (P<0.05). It also attenuated proinflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ; their mRNA and protein levels changed accordingly compared with the controls (P<0.05).
CXCR4 antagonist AMD3100 significantly suppressed inflammatory response and reduced blood-brain barrier disruption after MCAO. AMD3100 attenuated ischemia-induced acute inflammation by suppressing leukocyte migration and infiltration, in addition to reducing proinflammatory cytokine expression in the ischemic region.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - pathology</subject><subject>Brain Ischemia - drug therapy</subject><subject>Brain Ischemia - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Heterocyclic Compounds - pharmacology</subject><subject>Heterocyclic Compounds - therapeutic use</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Inflammation - prevention & control</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neurology</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Neutrophil Infiltration - drug effects</subject><subject>Neutrophil Infiltration - physiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, CXCR4 - antagonists & inhibitors</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpFkM1u1DAUhS0EokPhDRDyBolNin9ix15mhpaO2qrVUCR20R3npg0k8dT2LGbXl-AFeRJczUBXV-foO-dKh5D3nJ1wrvnnmIL_hXAPWYoTXTFh7Qsy40qURamFeUlmjElbiNLaI_Imxp-MMSGNek2OhOTalErOyOPix2JV0npKcOenPiZaX32RnDF6E3xClyKdD963fx5_zwP0E51DCD0GupwS3oU-7ShMLV1hu3UYs9sNMI6QfNhlM278FJHWXcqJM-9goMvo7nHsgeauq97hW_KqgyHiu8M9Jt_PTm8X58Xl9dflor4snGIsFYo5MNyAUMbptRVCI0plELnQdt1KyY11pVIaO81bu66U4R2rWlClgcqV8ph82vdugn_YYkzN2EeHwwAT-m1suKikUsIKk9Fyj7rgYwzYNZvQjxB2DWfN0_bNt9vV9cVpfV5nKZr99jn24fBhux6x_R_6N3YGPh4AiHmKLsDk-vjMVUxzZaz8C_N4jkE</recordid><startdate>2013</startdate><enddate>2013</enddate><creator>JUN HUANG</creator><creator>YANING LI</creator><creator>YAOHUI TANG</creator><creator>GUANGHUI TANG</creator><creator>YANG, Guo-Yuan</creator><creator>YONGTING WANG</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2013</creationdate><title>CXCR4 Antagonist AMD3100 Protects Blood―Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice</title><author>JUN HUANG ; YANING LI ; YAOHUI TANG ; GUANGHUI TANG ; YANG, Guo-Yuan ; YONGTING WANG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-50ca818a258c6b9226ee358ee1269bd33189c4556ef61d9b7581f07da548a7c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - pathology</topic><topic>Brain Ischemia - drug therapy</topic><topic>Brain Ischemia - metabolism</topic><topic>Brain Ischemia - pathology</topic><topic>Heterocyclic Compounds - pharmacology</topic><topic>Heterocyclic Compounds - therapeutic use</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Inflammation - prevention & control</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Neurology</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Neutrophil Infiltration - drug effects</topic><topic>Neutrophil Infiltration - physiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, CXCR4 - antagonists & inhibitors</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JUN HUANG</creatorcontrib><creatorcontrib>YANING LI</creatorcontrib><creatorcontrib>YAOHUI TANG</creatorcontrib><creatorcontrib>GUANGHUI TANG</creatorcontrib><creatorcontrib>YANG, Guo-Yuan</creatorcontrib><creatorcontrib>YONGTING WANG</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JUN HUANG</au><au>YANING LI</au><au>YAOHUI TANG</au><au>GUANGHUI TANG</au><au>YANG, Guo-Yuan</au><au>YONGTING WANG</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CXCR4 Antagonist AMD3100 Protects Blood―Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2013</date><risdate>2013</risdate><volume>44</volume><issue>1</issue><spage>190</spage><epage>197</epage><pages>190-197</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>Inflammatory response plays a critical role in propagating tissue damage after focal cerebral ischemia. CXCL12 is a key chemokine for leukocyte recruitment. However, the role of CXCL12 and its receptor CXCR4 in ischemia-induced inflammatory response is unclear. Here we use the pharmacological antagonist of CXCR4, AMD3100, to investigate the function of CXCL12/CXCR4 in regulating inflammatory response during acute ischemia.
Adult male CD-1 mice (n=184) underwent permanent suture middle cerebral artery occlusion (MCAO). AMD3100 was injected for 3 days (1 mg/kg/day) after MCAO. Brain water content, infarct volume, neurological score, and myeloperoxidase (MPO) expression and activity were examined at 24, 48, and 72 hours after MCAO. Proinflammatory cytokine RNA and protein levels in brain tissue were measured by RT-PCR and enzyme linked immunosorbent assay.
Neurological score was greatly improved in AMD3100-treated mice compared with the control mice 3 days after MCAO (P<0.05). Brain edema-induced change of water content, IgG protein leakage, Evans blue extravasation, occludin, and ZO-1 expression in ipsilateral hemisphere were alleviated by acute treatment of AMD3100. MPO expression and activity revealed that AMD3100 profoundly reduced the number of MPO-positive cells in the ischemic region (P<0.05). It also attenuated proinflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ; their mRNA and protein levels changed accordingly compared with the controls (P<0.05).
CXCR4 antagonist AMD3100 significantly suppressed inflammatory response and reduced blood-brain barrier disruption after MCAO. AMD3100 attenuated ischemia-induced acute inflammation by suppressing leukocyte migration and infiltration, in addition to reducing proinflammatory cytokine expression in the ischemic region.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>23168453</pmid><doi>10.1161/strokeaha.112.670299</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Stroke (1970), 2013, Vol.44 (1), p.190-197 |
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| source | Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Blood-Brain Barrier - drug effects Blood-Brain Barrier - pathology Brain Ischemia - drug therapy Brain Ischemia - metabolism Brain Ischemia - pathology Heterocyclic Compounds - pharmacology Heterocyclic Compounds - therapeutic use Inflammation - metabolism Inflammation - pathology Inflammation - prevention & control Male Medical sciences Mice Neurology Neuropharmacology Neuroprotective agent Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Neutrophil Infiltration - drug effects Neutrophil Infiltration - physiology Pharmacology. Drug treatments Receptors, CXCR4 - antagonists & inhibitors Vascular diseases and vascular malformations of the nervous system |
| title | CXCR4 Antagonist AMD3100 Protects Blood―Brain Barrier Integrity and Reduces Inflammatory Response After Focal Ischemia in Mice |
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