Neuroprotective effect of inhaled nitric oxide on excitotoxic-induced brain damage in neonatal rat
Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates. However, little information is known about its impact on the developing brain submitted to excitotoxic challenge. We investigated here the effect of iNO in a neonatal model of excitotoxic brain lesions. Rat pups and...
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| Veröffentlicht in: | PloS one 2010-06, Vol.5 (6), p.e10916-e10916 |
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| creator | Pansiot, Julien Loron, Gauthier Olivier, Paul Fontaine, Romain Charriaut-Marlangue, Christiane Mercier, Jean-Christophe Gressens, Pierre Baud, Olivier |
| description | Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates. However, little information is known about its impact on the developing brain submitted to excitotoxic challenge.
We investigated here the effect of iNO in a neonatal model of excitotoxic brain lesions. Rat pups and their dams were placed in a chamber containing 20 ppm NO during the first week of life. At postnatal day (P)5, rat pups were submitted to intracranial injection of glutamate agonists. At P10, rat pups exposed to iNO exhibited a significant decrease of lesion size in both the white matter and cortical plate compared to controls. Microglia activation and astrogliosis were found significantly decreased in NO-exposed animals. This neuroprotective effect was associated with a significant decrease of several glutamate receptor subunits expression at P5. iNO was associated with an early (P1) downregulation of pCREB/pAkt expression and induced an increase in pAkt protein concentration in response to excitotoxic challenge (P7).
This study is the first describe and investigate the neuroprotective effect of iNO in neonatal excitotoxic-induced brain damage. This effect may be mediated through CREB pathway and subsequent modulation of glutamate receptor subunits expression. |
| doi_str_mv | 10.1371/journal.pone.0010916 |
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This study is the first describe and investigate the neuroprotective effect of iNO in neonatal excitotoxic-induced brain damage. This effect may be mediated through CREB pathway and subsequent modulation of glutamate receptor subunits expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0010916</identifier><identifier>PMID: 20532231</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Administration, Inhalation ; Animals ; Animals, Newborn ; Brain ; Brain - drug effects ; Brain damage ; Brain injury ; Cortex ; Cyclic AMP response element-binding protein ; Excitation ; Excitotoxicity ; Gliosis ; Glutamate ; Glutamic acid receptors ; Kinases ; Lesions ; Magnetic Resonance Spectroscopy ; Microglia ; Neonates ; Neuroprotection ; Neuroprotective Agents - administration & dosage ; Neuroprotective Agents - pharmacology ; Neuroscience/Neurobiology of Disease and Regeneration ; Neuroscience/Neurodevelopment ; Newborn babies ; Nitric oxide ; Nitric Oxide - administration & dosage ; Nitric Oxide - pharmacology ; Pediatrics and Child Health/Neonatology ; Quantitative analysis ; Rats ; Rodents ; Substantia alba</subject><ispartof>PloS one, 2010-06, Vol.5 (6), p.e10916-e10916</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Pansiot et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Pansiot et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-64863b46e751fac1a6e47a6f20a604e0fbc29ea278fcd90fb4a218476657bd533</citedby><cites>FETCH-LOGICAL-c723t-64863b46e751fac1a6e47a6f20a604e0fbc29ea278fcd90fb4a218476657bd533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879374/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879374/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20532231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hashimoto, Kenji</contributor><creatorcontrib>Pansiot, Julien</creatorcontrib><creatorcontrib>Loron, Gauthier</creatorcontrib><creatorcontrib>Olivier, Paul</creatorcontrib><creatorcontrib>Fontaine, Romain</creatorcontrib><creatorcontrib>Charriaut-Marlangue, Christiane</creatorcontrib><creatorcontrib>Mercier, Jean-Christophe</creatorcontrib><creatorcontrib>Gressens, Pierre</creatorcontrib><creatorcontrib>Baud, Olivier</creatorcontrib><title>Neuroprotective effect of inhaled nitric oxide on excitotoxic-induced brain damage in neonatal rat</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates. However, little information is known about its impact on the developing brain submitted to excitotoxic challenge.
We investigated here the effect of iNO in a neonatal model of excitotoxic brain lesions. Rat pups and their dams were placed in a chamber containing 20 ppm NO during the first week of life. At postnatal day (P)5, rat pups were submitted to intracranial injection of glutamate agonists. At P10, rat pups exposed to iNO exhibited a significant decrease of lesion size in both the white matter and cortical plate compared to controls. Microglia activation and astrogliosis were found significantly decreased in NO-exposed animals. This neuroprotective effect was associated with a significant decrease of several glutamate receptor subunits expression at P5. iNO was associated with an early (P1) downregulation of pCREB/pAkt expression and induced an increase in pAkt protein concentration in response to excitotoxic challenge (P7).
This study is the first describe and investigate the neuroprotective effect of iNO in neonatal excitotoxic-induced brain damage. This effect may be mediated through CREB pathway and subsequent modulation of glutamate receptor subunits expression.</description><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Brain</subject><subject>Brain - drug effects</subject><subject>Brain damage</subject><subject>Brain injury</subject><subject>Cortex</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Excitation</subject><subject>Excitotoxicity</subject><subject>Gliosis</subject><subject>Glutamate</subject><subject>Glutamic acid receptors</subject><subject>Kinases</subject><subject>Lesions</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Microglia</subject><subject>Neonates</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - administration & dosage</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroscience/Neurobiology of Disease and Regeneration</subject><subject>Neuroscience/Neurodevelopment</subject><subject>Newborn babies</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - 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Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pansiot, Julien</au><au>Loron, Gauthier</au><au>Olivier, Paul</au><au>Fontaine, Romain</au><au>Charriaut-Marlangue, Christiane</au><au>Mercier, Jean-Christophe</au><au>Gressens, Pierre</au><au>Baud, Olivier</au><au>Hashimoto, Kenji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective effect of inhaled nitric oxide on excitotoxic-induced brain damage in neonatal rat</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>5</volume><issue>6</issue><spage>e10916</spage><epage>e10916</epage><pages>e10916-e10916</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates. However, little information is known about its impact on the developing brain submitted to excitotoxic challenge.
We investigated here the effect of iNO in a neonatal model of excitotoxic brain lesions. Rat pups and their dams were placed in a chamber containing 20 ppm NO during the first week of life. At postnatal day (P)5, rat pups were submitted to intracranial injection of glutamate agonists. At P10, rat pups exposed to iNO exhibited a significant decrease of lesion size in both the white matter and cortical plate compared to controls. Microglia activation and astrogliosis were found significantly decreased in NO-exposed animals. This neuroprotective effect was associated with a significant decrease of several glutamate receptor subunits expression at P5. iNO was associated with an early (P1) downregulation of pCREB/pAkt expression and induced an increase in pAkt protein concentration in response to excitotoxic challenge (P7).
This study is the first describe and investigate the neuroprotective effect of iNO in neonatal excitotoxic-induced brain damage. This effect may be mediated through CREB pathway and subsequent modulation of glutamate receptor subunits expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20532231</pmid><doi>10.1371/journal.pone.0010916</doi><tpages>e10916</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Inhalation Animals Animals, Newborn Brain Brain - drug effects Brain damage Brain injury Cortex Cyclic AMP response element-binding protein Excitation Excitotoxicity Gliosis Glutamate Glutamic acid receptors Kinases Lesions Magnetic Resonance Spectroscopy Microglia Neonates Neuroprotection Neuroprotective Agents - administration & dosage Neuroprotective Agents - pharmacology Neuroscience/Neurobiology of Disease and Regeneration Neuroscience/Neurodevelopment Newborn babies Nitric oxide Nitric Oxide - administration & dosage Nitric Oxide - pharmacology Pediatrics and Child Health/Neonatology Quantitative analysis Rats Rodents Substantia alba |
| title | Neuroprotective effect of inhaled nitric oxide on excitotoxic-induced brain damage in neonatal rat |
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