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Detection of Neuroinflammation in a Rat Model of Subarachnoid Hemorrhage Using [18F]DPA-714 PET Imaging

Identifieur interne : 002618 ( Pmc/Curation ); précédent : 002617; suivant : 002619

Detection of Neuroinflammation in a Rat Model of Subarachnoid Hemorrhage Using [18F]DPA-714 PET Imaging

Auteurs : Clément Thomas [France] ; Johnny Vercouillie [France] ; Aurélie Doméné [France] ; Clovis Tauber [France] ; Michael Kassiou [Australie] ; Denis Guilloteau [France] ; Christophe Destrieux [France] ; Sophie Sérrière [France] ; Sylvie Chalon [France]

Source :

RBID : PMC:5470081

Abstract

Subarachnoid hemorrhage (SAH) can lead to delayed cerebral ischemia, which increases the rate of morbidity and mortality. The detection of microglial activation may serve as a biomarker for the identification of patients at risk of this deleterious consequence. We assessed this hypothesis in a rat model of SAH in which the exploration of neuroinflammation related to microglial activation was correlated with the degree of bleeding. We used the rat filament model and evaluated (at 48 hours postsurgery) the intensity of neuroinflammation using positron emission tomography (PET) imaging with the 18-kDa translocator protein (TSPO) tracer [18F]DPA-714, quantitative autoradiography with [3H]PK-11195, and SAH grade by postmortem brain picture. High SAH grades were strongly and positively correlated with in vivo PET imaging of TSPO in the cortex and striatum. In addition, a positive correlation was found in the cortex in TSPO, with densities determined by imaging and autoradiographic approaches. Qualitative immunofluorescence studies indicated that overexpression of TSPO was linked to astrocytic/microglial activation. In this model, PET imaging of TSPO using [18F]DPA-714 appeared to be a relevant index of the degree of bleeding, indicating that this imaging method could be used in human patients to improve the management of patients with SAH.


Url:
DOI: 10.1177/1536012116639189
PubMed: 27118758
PubMed Central: 5470081

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PMC:5470081

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<p>Subarachnoid hemorrhage (SAH) can lead to delayed cerebral ischemia, which increases the rate of morbidity and mortality. The detection of microglial activation may serve as a biomarker for the identification of patients at risk of this deleterious consequence. We assessed this hypothesis in a rat model of SAH in which the exploration of neuroinflammation related to microglial activation was correlated with the degree of bleeding. We used the rat filament model and evaluated (at 48 hours postsurgery) the intensity of neuroinflammation using positron emission tomography (PET) imaging with the 18-kDa translocator protein (TSPO) tracer [
<sup>18</sup>
F]DPA-714, quantitative autoradiography with [
<sup>3</sup>
H]PK-11195, and SAH grade by postmortem brain picture. High SAH grades were strongly and positively correlated with in vivo PET imaging of TSPO in the cortex and striatum. In addition, a positive correlation was found in the cortex in TSPO, with densities determined by imaging and autoradiographic approaches. Qualitative immunofluorescence studies indicated that overexpression of TSPO was linked to astrocytic/microglial activation. In this model, PET imaging of TSPO using [
<sup>18</sup>
F]DPA-714 appeared to be a relevant index of the degree of bleeding, indicating that this imaging method could be used in human patients to improve the management of patients with SAH.</p>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Mol Imaging</journal-id>
<journal-id journal-id-type="iso-abbrev">Mol Imaging</journal-id>
<journal-id journal-id-type="publisher-id">MIX</journal-id>
<journal-id journal-id-type="hwp">spmix</journal-id>
<journal-title-group>
<journal-title>Molecular imaging</journal-title>
</journal-title-group>
<issn pub-type="ppub">1535-3508</issn>
<issn pub-type="epub">1536-0121</issn>
<publisher>
<publisher-name>SAGE Publications</publisher-name>
<publisher-loc>Sage CA: Los Angeles, CA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">27118758</article-id>
<article-id pub-id-type="pmc">5470081</article-id>
<article-id pub-id-type="doi">10.1177/1536012116639189</article-id>
<article-id pub-id-type="publisher-id">10.1177_1536012116639189</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Detection of Neuroinflammation in a Rat Model of Subarachnoid Hemorrhage Using [
<sup>18</sup>
F]DPA-714 PET Imaging</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Thomas</surname>
<given-names>Clément</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
<xref ref-type="aff" rid="aff2-1536012116639189">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vercouillie</surname>
<given-names>Johnny</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Doméné</surname>
<given-names>Aurélie</given-names>
</name>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tauber</surname>
<given-names>Clovis</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kassiou</surname>
<given-names>Michael</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="aff3-1536012116639189">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Guilloteau</surname>
<given-names>Denis</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
<xref ref-type="aff" rid="aff2-1536012116639189">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Destrieux</surname>
<given-names>Christophe</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
<xref ref-type="aff" rid="aff2-1536012116639189">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sérrière</surname>
<given-names>Sophie</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Chalon</surname>
<given-names>Sylvie</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="aff1-1536012116639189">1</xref>
<xref ref-type="corresp" rid="corresp1-1536012116639189"></xref>
</contrib>
</contrib-group>
<aff id="aff1-1536012116639189">
<label>1</label>
UMR Inserm U930, Université François-Rabelais de Tours, Tours, France</aff>
<aff id="aff2-1536012116639189">
<label>2</label>
CHRU de Tours, Tours, France</aff>
<aff id="aff3-1536012116639189">
<label>3</label>
Faculty of Health Sciences, School of Chemistry, University of Sydney, Sydney, Australia</aff>
<author-notes>
<corresp id="corresp1-1536012116639189">Sylvie Chalon, UMR Inserm U930, UFR de Médecine, 10 boulevard Tonnellé, 37032 Tours, France. Email:
<email>sylvie.chalon@univ-tours.fr</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>26</day>
<month>4</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection">
<season>Jan-Dec</season>
<year>2016</year>
</pub-date>
<volume>15</volume>
<elocation-id>1536012116639189</elocation-id>
<history>
<date date-type="received">
<day>30</day>
<month>7</month>
<year>2015</year>
</date>
<date date-type="rev-recd">
<day>8</day>
<month>12</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>16</day>
<month>12</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2016</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder content-type="sage">SAGE Publications Inc.</copyright-holder>
<license license-type="creative-commons" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
<license-p>This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (
<ext-link ext-link-type="uri" xlink:href="http://www.creativecommons.org/licenses/by-nc/3.0/">http://www.creativecommons.org/licenses/by-nc/3.0/</ext-link>
) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (
<ext-link ext-link-type="uri" xlink:href="https://us.sagepub.com/en-us/nam/open-access-at-sage">https://us.sagepub.com/en-us/nam/open-access-at-sage</ext-link>
).</license-p>
</license>
</permissions>
<abstract>
<p>Subarachnoid hemorrhage (SAH) can lead to delayed cerebral ischemia, which increases the rate of morbidity and mortality. The detection of microglial activation may serve as a biomarker for the identification of patients at risk of this deleterious consequence. We assessed this hypothesis in a rat model of SAH in which the exploration of neuroinflammation related to microglial activation was correlated with the degree of bleeding. We used the rat filament model and evaluated (at 48 hours postsurgery) the intensity of neuroinflammation using positron emission tomography (PET) imaging with the 18-kDa translocator protein (TSPO) tracer [
<sup>18</sup>
F]DPA-714, quantitative autoradiography with [
<sup>3</sup>
H]PK-11195, and SAH grade by postmortem brain picture. High SAH grades were strongly and positively correlated with in vivo PET imaging of TSPO in the cortex and striatum. In addition, a positive correlation was found in the cortex in TSPO, with densities determined by imaging and autoradiographic approaches. Qualitative immunofluorescence studies indicated that overexpression of TSPO was linked to astrocytic/microglial activation. In this model, PET imaging of TSPO using [
<sup>18</sup>
F]DPA-714 appeared to be a relevant index of the degree of bleeding, indicating that this imaging method could be used in human patients to improve the management of patients with SAH.</p>
</abstract>
<kwd-group>
<kwd>animal model</kwd>
<kwd>neuroinflammation</kwd>
<kwd>PET</kwd>
<kwd>SAH</kwd>
<kwd>TSPO</kwd>
</kwd-group>
<custom-meta-group>
<custom-meta>
<meta-name>cover-date</meta-name>
<meta-value>January-December 2016</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>

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