Inhibition of Neuroinflammation Prevents Injury to the Serotonergic Network After Hypoxia-Ischemia in the Immature Rat Brain
The phenotypic identities and characterization of neural networks disrupted after neonatal hypoxia-ischemia (HI) in the preterm brain remain to be elucidated. Interruption of the central serotonergic (5-hydroxytryptamine [5-HT]) system can lead to numerous functional deficits, many of which match th...
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| Veröffentlicht in: | Journal of neuropathology and experimental neurology 2011-01, Vol.70 (1), p.23-35 |
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| creator | Wixey, Julie A Reinebrant, Hanna E Buller, Kathryn M |
| description | The phenotypic identities and characterization of neural networks disrupted after neonatal hypoxia-ischemia (HI) in the preterm brain remain to be elucidated. Interruption of the central serotonergic (5-hydroxytryptamine [5-HT]) system can lead to numerous functional deficits, many of which match those in human preterm neonates exposedto HI. How the central serotonergic network is damaged after HIand mechanisms underlying such injury are not known. We used aPostnatal Day 3 rat model of preterm HI and found parallel reductionsin the 5-HT transporter expression, 5-HT levels and numbers of 5-HT-positive dorsal raphe neurons 1 week after insult. Post-HI administration of minocycline, an inhibitor of activated microglia, attenuated HI-induced damage to the serotonergic network. Minocycline effects seemed to be region specific, that is, where there was microglialactivation and increases in tumor necrosis factor-α and interleukin1β. The concurrent improvement in serotonergic outcomes suggests that inhibition of neuroinflammation prevented damage to theserotonergic neurons rather than affected the regulation of 5-HT orserotonin transporter. These data elucidate the mechanisms of serotonergic network injury in HI, and despite the known adverse effects associated with the use of minocycline in neonates, postinsult administration of minocycline may represent a novel approach to counter neuroinflammation and preserve the integrity of the central serotonergic network in the preterm neonate. |
| doi_str_mv | 10.1097/NEN.0b013e3182020b7b |
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Interruption of the central serotonergic (5-hydroxytryptamine [5-HT]) system can lead to numerous functional deficits, many of which match those in human preterm neonates exposedto HI. How the central serotonergic network is damaged after HIand mechanisms underlying such injury are not known. We used aPostnatal Day 3 rat model of preterm HI and found parallel reductionsin the 5-HT transporter expression, 5-HT levels and numbers of 5-HT-positive dorsal raphe neurons 1 week after insult. Post-HI administration of minocycline, an inhibitor of activated microglia, attenuated HI-induced damage to the serotonergic network. Minocycline effects seemed to be region specific, that is, where there was microglialactivation and increases in tumor necrosis factor-α and interleukin1β. The concurrent improvement in serotonergic outcomes suggests that inhibition of neuroinflammation prevented damage to theserotonergic neurons rather than affected the regulation of 5-HT orserotonin transporter. These data elucidate the mechanisms of serotonergic network injury in HI, and despite the known adverse effects associated with the use of minocycline in neonates, postinsult administration of minocycline may represent a novel approach to counter neuroinflammation and preserve the integrity of the central serotonergic network in the preterm neonate.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1097/NEN.0b013e3182020b7b</identifier><identifier>PMID: 21157380</identifier><identifier>CODEN: JNENAD</identifier><language>eng</language><publisher>Hagerstown, MD: American Association of Neuropathologists, Inc</publisher><subject>Alcoholism and acute alcohol poisoning ; Animals ; Animals, Newborn ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Biological and medical sciences ; Female ; Hypoxia-Ischemia, Brain - metabolism ; Hypoxia-Ischemia, Brain - pathology ; Hypoxia-Ischemia, Brain - prevention & control ; Inflammation - metabolism ; Inflammation - pathology ; Inflammation - prevention & control ; Inflammation Mediators - administration & dosage ; Inflammation Mediators - therapeutic use ; Medical sciences ; Minocycline - therapeutic use ; Nerve Net - drug effects ; Nerve Net - metabolism ; Nerve Net - pathology ; Neurology ; Prosencephalon - drug effects ; Prosencephalon - growth & development ; Prosencephalon - metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; RNA-Binding Proteins - physiology ; Serotonin - physiology ; Toxicology</subject><ispartof>Journal of neuropathology and experimental neurology, 2011-01, Vol.70 (1), p.23-35</ispartof><rights>2011 American Association of Neuropathologists, Inc</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Lippincott Williams & Wilkins Jan 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5203-d7d55dd337653c678766950a4a57b08bd707c9c7ad10b8500d9c0d2f3c241e763</citedby><cites>FETCH-LOGICAL-c5203-d7d55dd337653c678766950a4a57b08bd707c9c7ad10b8500d9c0d2f3c241e763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23740796$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21157380$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wixey, Julie A</creatorcontrib><creatorcontrib>Reinebrant, Hanna E</creatorcontrib><creatorcontrib>Buller, Kathryn M</creatorcontrib><title>Inhibition of Neuroinflammation Prevents Injury to the Serotonergic Network After Hypoxia-Ischemia in the Immature Rat Brain</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>The phenotypic identities and characterization of neural networks disrupted after neonatal hypoxia-ischemia (HI) in the preterm brain remain to be elucidated. Interruption of the central serotonergic (5-hydroxytryptamine [5-HT]) system can lead to numerous functional deficits, many of which match those in human preterm neonates exposedto HI. How the central serotonergic network is damaged after HIand mechanisms underlying such injury are not known. We used aPostnatal Day 3 rat model of preterm HI and found parallel reductionsin the 5-HT transporter expression, 5-HT levels and numbers of 5-HT-positive dorsal raphe neurons 1 week after insult. Post-HI administration of minocycline, an inhibitor of activated microglia, attenuated HI-induced damage to the serotonergic network. Minocycline effects seemed to be region specific, that is, where there was microglialactivation and increases in tumor necrosis factor-α and interleukin1β. The concurrent improvement in serotonergic outcomes suggests that inhibition of neuroinflammation prevented damage to theserotonergic neurons rather than affected the regulation of 5-HT orserotonin transporter. These data elucidate the mechanisms of serotonergic network injury in HI, and despite the known adverse effects associated with the use of minocycline in neonates, postinsult administration of minocycline may represent a novel approach to counter neuroinflammation and preserve the integrity of the central serotonergic network in the preterm neonate.</description><subject>Alcoholism and acute alcohol poisoning</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Biological and medical sciences</subject><subject>Female</subject><subject>Hypoxia-Ischemia, Brain - metabolism</subject><subject>Hypoxia-Ischemia, Brain - pathology</subject><subject>Hypoxia-Ischemia, Brain - prevention & control</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Inflammation - prevention & control</subject><subject>Inflammation Mediators - administration & dosage</subject><subject>Inflammation Mediators - therapeutic use</subject><subject>Medical sciences</subject><subject>Minocycline - therapeutic use</subject><subject>Nerve Net - drug effects</subject><subject>Nerve Net - metabolism</subject><subject>Nerve Net - pathology</subject><subject>Neurology</subject><subject>Prosencephalon - drug effects</subject><subject>Prosencephalon - growth & development</subject><subject>Prosencephalon - metabolism</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA-Binding Proteins - physiology</subject><subject>Serotonin - physiology</subject><subject>Toxicology</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkV1rFDEUhoModq3-A5EgiFdTT5LJZHJZS7UDZRU_rodMJuNkO5OsScZ1wR9vtl0t9Crk8LxvDnkQekngjIAU79aX6zPogDDDSE2BQie6R2hFOC-Liov6MVoBUFowqOQJehbjBgAkyPIpOqGEcMFqWKE_jRttZ5P1DvsBr80SvHXDpOZZ3Q4_B_PLuBRx4zZL2OPkcRoN_mqCT96Z8MPqnEo7H27w-ZBMwFf7rf9tVdFEPZrZKmzdbaQ5VC7B4C8q4fdBWfccPRnUFM2L43mKvn-4_HZxVVx_-thcnF8XmlNgRS96zvueMVFxpitRi6qSHFSpuOig7noBQkstVE-gqzlALzX0dGCalsSIip2it3e92-B_LiamdrZRm2lSzvgltjVnlZCE8ky-fkBu_BJcXq6tS0FpzaXMUHkH6eBjDGZot8HOKuxbAu3BTZvdtA_d5NirY_fSzab_H_onIwNvjoCKWk1DUE7beM8xUYKQ1f37Oz_lD48307IzoR2NmtLYZsvAQdCCAiFA8q04jBj7CwnPp8M</recordid><startdate>201101</startdate><enddate>201101</enddate><creator>Wixey, Julie A</creator><creator>Reinebrant, Hanna E</creator><creator>Buller, Kathryn M</creator><general>American Association of Neuropathologists, Inc</general><general>Lippincott Williams & Wilkins</general><general>Oxford University Press</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>201101</creationdate><title>Inhibition of Neuroinflammation Prevents Injury to the Serotonergic Network After Hypoxia-Ischemia in the Immature Rat Brain</title><author>Wixey, Julie A ; Reinebrant, Hanna E ; Buller, Kathryn M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5203-d7d55dd337653c678766950a4a57b08bd707c9c7ad10b8500d9c0d2f3c241e763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Alcoholism and acute alcohol poisoning</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Biological and medical sciences</topic><topic>Female</topic><topic>Hypoxia-Ischemia, Brain - metabolism</topic><topic>Hypoxia-Ischemia, Brain - pathology</topic><topic>Hypoxia-Ischemia, Brain - prevention & control</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Inflammation - prevention & control</topic><topic>Inflammation Mediators - administration & dosage</topic><topic>Inflammation Mediators - therapeutic use</topic><topic>Medical sciences</topic><topic>Minocycline - therapeutic use</topic><topic>Nerve Net - drug effects</topic><topic>Nerve Net - metabolism</topic><topic>Nerve Net - pathology</topic><topic>Neurology</topic><topic>Prosencephalon - drug effects</topic><topic>Prosencephalon - growth & development</topic><topic>Prosencephalon - metabolism</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA-Binding Proteins - physiology</topic><topic>Serotonin - physiology</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wixey, Julie A</creatorcontrib><creatorcontrib>Reinebrant, Hanna E</creatorcontrib><creatorcontrib>Buller, Kathryn M</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>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wixey, Julie A</au><au>Reinebrant, Hanna E</au><au>Buller, Kathryn M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Neuroinflammation Prevents Injury to the Serotonergic Network After Hypoxia-Ischemia in the Immature Rat Brain</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2011-01</date><risdate>2011</risdate><volume>70</volume><issue>1</issue><spage>23</spage><epage>35</epage><pages>23-35</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><coden>JNENAD</coden><abstract>The phenotypic identities and characterization of neural networks disrupted after neonatal hypoxia-ischemia (HI) in the preterm brain remain to be elucidated. Interruption of the central serotonergic (5-hydroxytryptamine [5-HT]) system can lead to numerous functional deficits, many of which match those in human preterm neonates exposedto HI. How the central serotonergic network is damaged after HIand mechanisms underlying such injury are not known. We used aPostnatal Day 3 rat model of preterm HI and found parallel reductionsin the 5-HT transporter expression, 5-HT levels and numbers of 5-HT-positive dorsal raphe neurons 1 week after insult. Post-HI administration of minocycline, an inhibitor of activated microglia, attenuated HI-induced damage to the serotonergic network. Minocycline effects seemed to be region specific, that is, where there was microglialactivation and increases in tumor necrosis factor-α and interleukin1β. The concurrent improvement in serotonergic outcomes suggests that inhibition of neuroinflammation prevented damage to theserotonergic neurons rather than affected the regulation of 5-HT orserotonin transporter. These data elucidate the mechanisms of serotonergic network injury in HI, and despite the known adverse effects associated with the use of minocycline in neonates, postinsult administration of minocycline may represent a novel approach to counter neuroinflammation and preserve the integrity of the central serotonergic network in the preterm neonate.</abstract><cop>Hagerstown, MD</cop><pub>American Association of Neuropathologists, Inc</pub><pmid>21157380</pmid><doi>10.1097/NEN.0b013e3182020b7b</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | Journals@Ovid Ovid Autoload; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Alcoholism and acute alcohol poisoning Animals Animals, Newborn Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Biological and medical sciences Female Hypoxia-Ischemia, Brain - metabolism Hypoxia-Ischemia, Brain - pathology Hypoxia-Ischemia, Brain - prevention & control Inflammation - metabolism Inflammation - pathology Inflammation - prevention & control Inflammation Mediators - administration & dosage Inflammation Mediators - therapeutic use Medical sciences Minocycline - therapeutic use Nerve Net - drug effects Nerve Net - metabolism Nerve Net - pathology Neurology Prosencephalon - drug effects Prosencephalon - growth & development Prosencephalon - metabolism Random Allocation Rats Rats, Sprague-Dawley RNA-Binding Proteins - physiology Serotonin - physiology Toxicology |
| title | Inhibition of Neuroinflammation Prevents Injury to the Serotonergic Network After Hypoxia-Ischemia in the Immature Rat Brain |
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