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Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic-ischemic brain injury in the neonatal male rat
•GB alleviated hypoxic-ischemic brain injury in the neonatal male rat.•GB treatment dramatically suppressed microglia activation and NLRP3 expression.•GB pretreatment significantly inhibited signal 1 and signal 2 of NLRP3 inflammasome activation. Perinatal hypoxic-ischemic (HI) insult is an importan...
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| Published in: | International journal of developmental neuroscience 2018-10, Vol.69 (1), p.106-111 |
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| creator | Chen, Aiming Xu, Yin Yuan, Jun |
| description | •GB alleviated hypoxic-ischemic brain injury in the neonatal male rat.•GB treatment dramatically suppressed microglia activation and NLRP3 expression.•GB pretreatment significantly inhibited signal 1 and signal 2 of NLRP3 inflammasome activation.
Perinatal hypoxic-ischemic (HI) insult is an important cause of brain injury in neonates. The development of novel treatment strategies for neonates with HI brain injury is urgently needed. Ginkgolide B (GB) is a main component of Ginkgo biloba extracts with a long history of use in traditional Chinese medicine. However, it is unknown whether GB could play a protective role in hypoxic stress in immature animals.
Using neonatal hypoxic-ischemic (HI) brain injury model of rat pups, neurological score, infarct size, and brain edema were evaluated after HI injury. The activation of microglia and the production of IL-1β and IL-18 were detected by immunohistochemistry and ELISA, respectively. A priming signal (NF-κB P65) and an activation signal (Caspase-1) of NLRP3 inflammasome activation were detected by western blot analyses.
GB administrated 30 min prior to ischemia induction can improve neurological disorder, reduce infarct volume and alleviate cerebral edema. Compared with the HI groups, GB inhibited the activation of microglia and decreased the production of IL-1β and IL-18 in neocortex. Furthermore, GB reduced NLRP3 expression mainly in microglia, and significantly inhibited the expression of Caspase-1 and the nuclear translocation of NF-κB P65, preventing NLRP3 inflammasome activation.
GB ameliorates hypoxic-ischemic brain injury in the neonatal male rat via inhibiting NLRP3 inflammasome activation. |
| doi_str_mv | 10.1016/j.ijdevneu.2018.07.004 |
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Perinatal hypoxic-ischemic (HI) insult is an important cause of brain injury in neonates. The development of novel treatment strategies for neonates with HI brain injury is urgently needed. Ginkgolide B (GB) is a main component of Ginkgo biloba extracts with a long history of use in traditional Chinese medicine. However, it is unknown whether GB could play a protective role in hypoxic stress in immature animals.
Using neonatal hypoxic-ischemic (HI) brain injury model of rat pups, neurological score, infarct size, and brain edema were evaluated after HI injury. The activation of microglia and the production of IL-1β and IL-18 were detected by immunohistochemistry and ELISA, respectively. A priming signal (NF-κB P65) and an activation signal (Caspase-1) of NLRP3 inflammasome activation were detected by western blot analyses.
GB administrated 30 min prior to ischemia induction can improve neurological disorder, reduce infarct volume and alleviate cerebral edema. Compared with the HI groups, GB inhibited the activation of microglia and decreased the production of IL-1β and IL-18 in neocortex. Furthermore, GB reduced NLRP3 expression mainly in microglia, and significantly inhibited the expression of Caspase-1 and the nuclear translocation of NF-κB P65, preventing NLRP3 inflammasome activation.
GB ameliorates hypoxic-ischemic brain injury in the neonatal male rat via inhibiting NLRP3 inflammasome activation.</description><identifier>ISSN: 0736-5748</identifier><identifier>EISSN: 1873-474X</identifier><identifier>DOI: 10.1016/j.ijdevneu.2018.07.004</identifier><identifier>PMID: 30030129</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Animals ; Animals, Newborn ; Behavior, Animal ; Brain ; Brain Edema - etiology ; Brain Edema - pathology ; Brain Infarction - pathology ; Brain injury ; Caspase ; Caspase 1 - biosynthesis ; Caspase 1 - drug effects ; Caspase-1 ; Edema ; Enzyme-linked immunosorbent assay ; Female ; Free Radical Scavengers - pharmacology ; Ginkgo biloba ; Ginkgolide B ; Ginkgolides - pharmacology ; Head injuries ; Herbal medicine ; Hypoxia ; Hypoxia-Ischemia, Brain - pathology ; Hypoxia-Ischemia, Brain - psychology ; IL-1β ; Immunohistochemistry ; Inflammasomes ; Inflammasomes - drug effects ; Injury prevention ; Interleukin 18 ; Interleukin-18 - biosynthesis ; Interleukin-1beta - biosynthesis ; Ischemia ; Lactones - pharmacology ; Macrophage Activation - drug effects ; Male ; Microglia ; Microglia - drug effects ; Neocortex ; Neonatal hypoxic-ischemic encephalopathy ; Neonates ; Neurological disorders ; NF-κB protein ; NLR Family, Pyrin Domain-Containing 3 Protein - drug effects ; NLRP3 inflammasome ; Nuclear transport ; Pregnancy ; Priming ; Rats ; Traditional Chinese medicine ; Transcription Factor RelA - biosynthesis ; Translocation ; Traumatic brain injury</subject><ispartof>International journal of developmental neuroscience, 2018-10, Vol.69 (1), p.106-111</ispartof><rights>2018</rights><rights>2018 ISDN</rights><rights>Copyright © 2018. Published by Elsevier Ltd.</rights><rights>Copyright Elsevier BV Oct 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5764-3a66cf73838faeb0401ffed411abaae1e7b3bcd55a305fbaf524ed1c4f53edea3</citedby><cites>FETCH-LOGICAL-c5764-3a66cf73838faeb0401ffed411abaae1e7b3bcd55a305fbaf524ed1c4f53edea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30030129$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Aiming</creatorcontrib><creatorcontrib>Xu, Yin</creatorcontrib><creatorcontrib>Yuan, Jun</creatorcontrib><title>Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic-ischemic brain injury in the neonatal male rat</title><title>International journal of developmental neuroscience</title><addtitle>Int J Dev Neurosci</addtitle><description>•GB alleviated hypoxic-ischemic brain injury in the neonatal male rat.•GB treatment dramatically suppressed microglia activation and NLRP3 expression.•GB pretreatment significantly inhibited signal 1 and signal 2 of NLRP3 inflammasome activation.
Perinatal hypoxic-ischemic (HI) insult is an important cause of brain injury in neonates. The development of novel treatment strategies for neonates with HI brain injury is urgently needed. Ginkgolide B (GB) is a main component of Ginkgo biloba extracts with a long history of use in traditional Chinese medicine. However, it is unknown whether GB could play a protective role in hypoxic stress in immature animals.
Using neonatal hypoxic-ischemic (HI) brain injury model of rat pups, neurological score, infarct size, and brain edema were evaluated after HI injury. The activation of microglia and the production of IL-1β and IL-18 were detected by immunohistochemistry and ELISA, respectively. A priming signal (NF-κB P65) and an activation signal (Caspase-1) of NLRP3 inflammasome activation were detected by western blot analyses.
GB administrated 30 min prior to ischemia induction can improve neurological disorder, reduce infarct volume and alleviate cerebral edema. Compared with the HI groups, GB inhibited the activation of microglia and decreased the production of IL-1β and IL-18 in neocortex. Furthermore, GB reduced NLRP3 expression mainly in microglia, and significantly inhibited the expression of Caspase-1 and the nuclear translocation of NF-κB P65, preventing NLRP3 inflammasome activation.
GB ameliorates hypoxic-ischemic brain injury in the neonatal male rat via inhibiting NLRP3 inflammasome activation.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Behavior, Animal</subject><subject>Brain</subject><subject>Brain Edema - etiology</subject><subject>Brain Edema - pathology</subject><subject>Brain Infarction - pathology</subject><subject>Brain injury</subject><subject>Caspase</subject><subject>Caspase 1 - biosynthesis</subject><subject>Caspase 1 - drug effects</subject><subject>Caspase-1</subject><subject>Edema</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Ginkgo biloba</subject><subject>Ginkgolide B</subject><subject>Ginkgolides - pharmacology</subject><subject>Head injuries</subject><subject>Herbal medicine</subject><subject>Hypoxia</subject><subject>Hypoxia-Ischemia, Brain - pathology</subject><subject>Hypoxia-Ischemia, Brain - psychology</subject><subject>IL-1β</subject><subject>Immunohistochemistry</subject><subject>Inflammasomes</subject><subject>Inflammasomes - drug effects</subject><subject>Injury prevention</subject><subject>Interleukin 18</subject><subject>Interleukin-18 - biosynthesis</subject><subject>Interleukin-1beta - biosynthesis</subject><subject>Ischemia</subject><subject>Lactones - pharmacology</subject><subject>Macrophage Activation - drug effects</subject><subject>Male</subject><subject>Microglia</subject><subject>Microglia - drug effects</subject><subject>Neocortex</subject><subject>Neonatal hypoxic-ischemic encephalopathy</subject><subject>Neonates</subject><subject>Neurological disorders</subject><subject>NF-κB protein</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - drug effects</subject><subject>NLRP3 inflammasome</subject><subject>Nuclear transport</subject><subject>Pregnancy</subject><subject>Priming</subject><subject>Rats</subject><subject>Traditional Chinese medicine</subject><subject>Transcription Factor RelA - biosynthesis</subject><subject>Translocation</subject><subject>Traumatic brain injury</subject><issn>0736-5748</issn><issn>1873-474X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqNkUFv1DAQhSMEokvhL1SWuHBJsGMnTm9Au5RdrRaEKOJmTZwx65DEWztZ2H-PV2k5cIHTSKPvvXmalyQXjGaMsvJ1m9m2wcOAU5ZTVmVUZpSKR8mCVZKnQopvj5MFlbxMCymqs-RZCC2ltCioeJqccUo5ZfnlIgk3dvjx3XW2QfKOQI-ddR5GDGS7-fyJEzuYDvoeguuRgB7tAUbrBgJmRE92x737ZXVqg95hbzWpPdghitrJH-Mg4w7JgG6AETrSQ4ckmj9PnhjoAr64n-fJ7fvll6sP6ebjzerq7SbVhSxFyqEstZG84pUBrKmgzBhsBGNQAyBDWfNaN0UBnBamBlPkAhumhSk4Ngj8PHk1--69u5swjKqPQbHrIEaagsrjfziXl6yM6Mu_0NZNfojpVM5YWeaikiJS5Uxp70LwaNTe2x78UTGqTrWoVj3Uok61KCpVrCUKL-7tp7rH5o_soYcIrGbgp-3w-J-2an29Xa_W18uv2-XtaU_lfOzN7IXxtweLXgVtcdDYWI96VI2z_8r7G-_Yuow</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Chen, Aiming</creator><creator>Xu, Yin</creator><creator>Yuan, Jun</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><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>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201810</creationdate><title>Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic-ischemic brain injury in the neonatal male rat</title><author>Chen, Aiming ; Xu, Yin ; Yuan, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5764-3a66cf73838faeb0401ffed411abaae1e7b3bcd55a305fbaf524ed1c4f53edea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Behavior, Animal</topic><topic>Brain</topic><topic>Brain Edema - etiology</topic><topic>Brain Edema - pathology</topic><topic>Brain Infarction - pathology</topic><topic>Brain injury</topic><topic>Caspase</topic><topic>Caspase 1 - biosynthesis</topic><topic>Caspase 1 - drug effects</topic><topic>Caspase-1</topic><topic>Edema</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Ginkgo biloba</topic><topic>Ginkgolide B</topic><topic>Ginkgolides - pharmacology</topic><topic>Head injuries</topic><topic>Herbal medicine</topic><topic>Hypoxia</topic><topic>Hypoxia-Ischemia, Brain - pathology</topic><topic>Hypoxia-Ischemia, Brain - psychology</topic><topic>IL-1β</topic><topic>Immunohistochemistry</topic><topic>Inflammasomes</topic><topic>Inflammasomes - drug effects</topic><topic>Injury prevention</topic><topic>Interleukin 18</topic><topic>Interleukin-18 - biosynthesis</topic><topic>Interleukin-1beta - biosynthesis</topic><topic>Ischemia</topic><topic>Lactones - pharmacology</topic><topic>Macrophage Activation - drug effects</topic><topic>Male</topic><topic>Microglia</topic><topic>Microglia - drug effects</topic><topic>Neocortex</topic><topic>Neonatal hypoxic-ischemic encephalopathy</topic><topic>Neonates</topic><topic>Neurological disorders</topic><topic>NF-κB protein</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - drug effects</topic><topic>NLRP3 inflammasome</topic><topic>Nuclear transport</topic><topic>Pregnancy</topic><topic>Priming</topic><topic>Rats</topic><topic>Traditional Chinese medicine</topic><topic>Transcription Factor RelA - biosynthesis</topic><topic>Translocation</topic><topic>Traumatic brain injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Aiming</creatorcontrib><creatorcontrib>Xu, Yin</creatorcontrib><creatorcontrib>Yuan, Jun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of developmental neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Aiming</au><au>Xu, Yin</au><au>Yuan, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic-ischemic brain injury in the neonatal male rat</atitle><jtitle>International journal of developmental neuroscience</jtitle><addtitle>Int J Dev Neurosci</addtitle><date>2018-10</date><risdate>2018</risdate><volume>69</volume><issue>1</issue><spage>106</spage><epage>111</epage><pages>106-111</pages><issn>0736-5748</issn><eissn>1873-474X</eissn><abstract>•GB alleviated hypoxic-ischemic brain injury in the neonatal male rat.•GB treatment dramatically suppressed microglia activation and NLRP3 expression.•GB pretreatment significantly inhibited signal 1 and signal 2 of NLRP3 inflammasome activation.
Perinatal hypoxic-ischemic (HI) insult is an important cause of brain injury in neonates. The development of novel treatment strategies for neonates with HI brain injury is urgently needed. Ginkgolide B (GB) is a main component of Ginkgo biloba extracts with a long history of use in traditional Chinese medicine. However, it is unknown whether GB could play a protective role in hypoxic stress in immature animals.
Using neonatal hypoxic-ischemic (HI) brain injury model of rat pups, neurological score, infarct size, and brain edema were evaluated after HI injury. The activation of microglia and the production of IL-1β and IL-18 were detected by immunohistochemistry and ELISA, respectively. A priming signal (NF-κB P65) and an activation signal (Caspase-1) of NLRP3 inflammasome activation were detected by western blot analyses.
GB administrated 30 min prior to ischemia induction can improve neurological disorder, reduce infarct volume and alleviate cerebral edema. Compared with the HI groups, GB inhibited the activation of microglia and decreased the production of IL-1β and IL-18 in neocortex. Furthermore, GB reduced NLRP3 expression mainly in microglia, and significantly inhibited the expression of Caspase-1 and the nuclear translocation of NF-κB P65, preventing NLRP3 inflammasome activation.
GB ameliorates hypoxic-ischemic brain injury in the neonatal male rat via inhibiting NLRP3 inflammasome activation.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>30030129</pmid><doi>10.1016/j.ijdevneu.2018.07.004</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Animals, Newborn Behavior, Animal Brain Brain Edema - etiology Brain Edema - pathology Brain Infarction - pathology Brain injury Caspase Caspase 1 - biosynthesis Caspase 1 - drug effects Caspase-1 Edema Enzyme-linked immunosorbent assay Female Free Radical Scavengers - pharmacology Ginkgo biloba Ginkgolide B Ginkgolides - pharmacology Head injuries Herbal medicine Hypoxia Hypoxia-Ischemia, Brain - pathology Hypoxia-Ischemia, Brain - psychology IL-1β Immunohistochemistry Inflammasomes Inflammasomes - drug effects Injury prevention Interleukin 18 Interleukin-18 - biosynthesis Interleukin-1beta - biosynthesis Ischemia Lactones - pharmacology Macrophage Activation - drug effects Male Microglia Microglia - drug effects Neocortex Neonatal hypoxic-ischemic encephalopathy Neonates Neurological disorders NF-κB protein NLR Family, Pyrin Domain-Containing 3 Protein - drug effects NLRP3 inflammasome Nuclear transport Pregnancy Priming Rats Traditional Chinese medicine Transcription Factor RelA - biosynthesis Translocation Traumatic brain injury |
| title | Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic-ischemic brain injury in the neonatal male rat |
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