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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand</title><author><name sortKey="Bekar, Lane K" sort="Bekar, Lane K" uniqKey="Bekar L" first="Lane K" last="Bekar">Lane K. Bekar</name><affiliation><nlm:aff id="aff1"><institution>Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center</institution>, Rochester, New York,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Wei, Helen S" sort="Wei, Helen S" uniqKey="Wei H" first="Helen S" last="Wei">Helen S. Wei</name><affiliation><nlm:aff id="aff1"><institution>Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center</institution>, Rochester, New York,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Nedergaard, Maiken" sort="Nedergaard, Maiken" uniqKey="Nedergaard M" first="Maiken" last="Nedergaard">Maiken Nedergaard</name><affiliation><nlm:aff id="aff1"><institution>Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center</institution>, Rochester, New York,<country>USA</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22872230</idno><idno type="pmc">3519408</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519408</idno><idno type="RBID">PMC:3519408</idno><idno type="doi">10.1038/jcbfm.2012.115</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000008</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000008</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand</title><author><name sortKey="Bekar, Lane K" sort="Bekar, Lane K" uniqKey="Bekar L" first="Lane K" last="Bekar">Lane K. Bekar</name><affiliation><nlm:aff id="aff1"><institution>Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center</institution>, Rochester, New York,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Wei, Helen S" sort="Wei, Helen S" uniqKey="Wei H" first="Helen S" last="Wei">Helen S. Wei</name><affiliation><nlm:aff id="aff1"><institution>Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center</institution>, Rochester, New York,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Nedergaard, Maiken" sort="Nedergaard, Maiken" uniqKey="Nedergaard M" first="Maiken" last="Nedergaard">Maiken Nedergaard</name><affiliation><nlm:aff id="aff1"><institution>Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center</institution>, Rochester, New York,<country>USA</country></nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Cerebral Blood Flow & Metabolism</title><idno type="ISSN">0271-678X</idno><idno type="eISSN">1559-7016</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Given the brain's uniquely high cell density and tissue oxygen levels bordering on hypoxia, the ability to rapidly and precisely match blood flow to constantly changing patterns in neural activity is an essential feature of cerebrovascular regulation. Locus coeruleus-norepinephrine (LC-NE) projections innervate the cerebral vasculature and can mediate vasoconstriction. However, function of the LC-mediated constriction in blood-flow regulation has never been addressed. Here, using intrinsic optical imaging coupled with an anesthesia regimen that only minimally interferes with LC activity, we show that NE enhances spatial and temporal aspects of functional hyperemia in the mouse somatosensory cortex. Increasing NE levels in the cortex using an <italic>α</italic><sub>2</sub>-adrenergic receptor antagonist paradoxically <italic>reduces</italic> the extent of functional hyperemia while enhancing the surround blood-flow reduction. However, the NE-mediated vasoconstriction optimizes spatial and temporal focusing of the hyperemic response resulting in a sixfold decrease in the disparity between blood volume and oxygen demand. In addition, NE-mediated vasoconstriction accelerated redistribution to subsequently active regions, enhancing temporal synchronization of blood delivery. These observations show an important role for NE in optimizing neurovascular coupling. As LC neuron loss is prominent in Alzheimer and Parkinson diseases, the diminished ability to couple blood volume to oxygen demand may contribute to their pathogenesis.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Cereb Blood Flow Metab</journal-id><journal-id journal-id-type="iso-abbrev">J. Cereb. Blood Flow Metab</journal-id><journal-title-group><journal-title>Journal of Cerebral Blood Flow & Metabolism</journal-title></journal-title-group><issn pub-type="ppub">0271-678X</issn><issn pub-type="epub">1559-7016</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22872230</article-id><article-id pub-id-type="pmc">3519408</article-id><article-id pub-id-type="pii">jcbfm2012115</article-id><article-id pub-id-type="doi">10.1038/jcbfm.2012.115</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand</article-title><alt-title alt-title-type="running">NE optimizes functional blood volume distribution</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Bekar</surname><given-names>Lane K</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><contrib contrib-type="author"><name><surname>Wei</surname><given-names>Helen S</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Nedergaard</surname><given-names>Maiken</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><aff id="aff1"><label>1</label><institution>Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center</institution>, Rochester, New York,<country>USA</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label><institution>Neural Systems and Plasticity Research Group, Department of Pharmacology, University of Saskatchewan</institution>, Saskatoon, SK, <country>Canada</country> S7N 5E5. E-mail: <email>lane.bekar@usask.ca</email></corresp></author-notes><pub-date pub-type="ppub"><month>12</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>08</day><month>08</month><year>2012</year></pub-date><volume>32</volume><issue>12</issue><fpage>2135</fpage><lpage>2145</lpage><history><date date-type="received"><day>18</day><month>04</month><year>2012</year></date><date date-type="rev-recd"><day>03</day><month>07</month><year>2012</year></date><date date-type="accepted"><day>04</day><month>07</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012 International Society for Cerebral Blood Flow & Metabolism, Inc.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>International Society for Cerebral Blood Flow & Metabolism, Inc.</copyright-holder></permissions><abstract><p>Given the brain's uniquely high cell density and tissue oxygen levels bordering on hypoxia, the ability to rapidly and precisely match blood flow to constantly changing patterns in neural activity is an essential feature of cerebrovascular regulation. Locus coeruleus-norepinephrine (LC-NE) projections innervate the cerebral vasculature and can mediate vasoconstriction. However, function of the LC-mediated constriction in blood-flow regulation has never been addressed. Here, using intrinsic optical imaging coupled with an anesthesia regimen that only minimally interferes with LC activity, we show that NE enhances spatial and temporal aspects of functional hyperemia in the mouse somatosensory cortex. Increasing NE levels in the cortex using an <italic>α</italic><sub>2</sub>-adrenergic receptor antagonist paradoxically <italic>reduces</italic> the extent of functional hyperemia while enhancing the surround blood-flow reduction. However, the NE-mediated vasoconstriction optimizes spatial and temporal focusing of the hyperemic response resulting in a sixfold decrease in the disparity between blood volume and oxygen demand. In addition, NE-mediated vasoconstriction accelerated redistribution to subsequently active regions, enhancing temporal synchronization of blood delivery. These observations show an important role for NE in optimizing neurovascular coupling. As LC neuron loss is prominent in Alzheimer and Parkinson diseases, the diminished ability to couple blood volume to oxygen demand may contribute to their pathogenesis.</p></abstract><kwd-group><kwd>cerebral hemodynamics</kwd><kwd>intrinsic optical imaging</kwd><kwd>neurovascular coupling</kwd><kwd>optical imaging</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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