Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases
Identifieur interne : 002E56 ( Main/Exploration ); précédent : 002E55; suivant : 002E57Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases
Auteurs : Christopher Power [Canada] ; Scot Henry ; Marc R. Del Bigio ; Peter H. Larsen ; Dale Corbett [Canada] ; Yumi Imai [Japon] ; Voon Wee Yong ; James Peeling [Canada]Source :
- Annals of Neurology [ 0364-5134 ] ; 2003-06.
Abstract
Intracerebral hemorrhage (ICH) is characterized by parenchymal hematoma formation with surrounding inflammation. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of neurological diseases defined by inflammation and cell death. To investigate the expression profile and pathogenic aspects of MMPs in ICH, we examined MMP expression in vivo using a collagenase‐induced rat model of ICH. ICH increased brain MMP‐2, ‐3, ‐7, and ‐9 mRNA levels relative to sham‐injected (control) animals in the vicinity of the hematoma, but MMP‐12 (macrophage metalloelastase) was the most highly induced MMP (>80‐fold). Immunohistochemistry showed MMP‐12 to be localized in activated monocytoid cells surrounding the hematoma. In vitro studies showed that thrombin, released during ICH, induced MMP‐12 expression in monocytoid cells, which was reduced by minocycline application. Similarly, in vivo minocycline treatment significantly reduced MMP‐12 levels in brain. Neuropathological studies disclosed marked glial activation and apoptosis after ICH that was reduced by minocycline treatment. Neurobehavioral outcomes also were improved with minocycline treatment compared with untreated ICH controls. Thus, select MMPs exhibit increased expression after ICH, whereas minocycline is neuroprotective after ICH by suppressing monocytoid cell activation and downregulating MMP‐12 expression.Ann Neurol 2003;53:731–742
Url:
DOI: 10.1002/ana.10553
Affiliations:
- Canada, Japon
- Alberta, Manitoba
- Calgary, Tokyo, Winnipeg
- Université de Calgary, Université du Manitoba
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Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of neurological diseases defined by inflammation and cell death. To investigate the expression profile and pathogenic aspects of MMPs in ICH, we examined MMP expression in vivo using a collagenase‐induced rat model of ICH. ICH increased brain MMP‐2, ‐3, ‐7, and ‐9 mRNA levels relative to sham‐injected (control) animals in the vicinity of the hematoma, but MMP‐12 (macrophage metalloelastase) was the most highly induced MMP (>80‐fold). Immunohistochemistry showed MMP‐12 to be localized in activated monocytoid cells surrounding the hematoma. In vitro studies showed that thrombin, released during ICH, induced MMP‐12 expression in monocytoid cells, which was reduced by minocycline application. Similarly, in vivo minocycline treatment significantly reduced MMP‐12 levels in brain. Neuropathological studies disclosed marked glial activation and apoptosis after ICH that was reduced by minocycline treatment. Neurobehavioral outcomes also were improved with minocycline treatment compared with untreated ICH controls. Thus, select MMPs exhibit increased expression after ICH, whereas minocycline is neuroprotective after ICH by suppressing monocytoid cell activation and downregulating MMP‐12 expression.Ann Neurol 2003;53:731–742</div></front></TEI><affiliations><list><country><li>Canada</li><li>Japon</li></country><region><li>Alberta</li><li>Manitoba</li></region><settlement><li>Calgary</li><li>Tokyo</li><li>Winnipeg</li></settlement><orgName><li>Université de Calgary</li><li>Université du Manitoba</li></orgName></list><tree><noCountry><name sortKey="Del Bigio, Marc R" sort="Del Bigio, Marc R" uniqKey="Del Bigio M" first="Marc R." last="Del Bigio">Marc R. Del Bigio</name><name sortKey="Henry, Scot" sort="Henry, Scot" uniqKey="Henry S" first="Scot" last="Henry">Scot Henry</name><name sortKey="Larsen, Peter H" sort="Larsen, Peter H" uniqKey="Larsen P" first="Peter H." last="Larsen">Peter H. Larsen</name><name sortKey="Yong, Voon Wee" sort="Yong, Voon Wee" uniqKey="Yong V" first="Voon Wee" last="Yong">Voon Wee Yong</name></noCountry><country name="Canada"><region name="Alberta"><name sortKey="Power, Christopher" sort="Power, Christopher" uniqKey="Power C" first="Christopher" last="Power">Christopher Power</name></region><name sortKey="Corbett, Dale" sort="Corbett, Dale" uniqKey="Corbett D" first="Dale" last="Corbett">Dale Corbett</name><name sortKey="Peeling, James" sort="Peeling, James" uniqKey="Peeling J" first="James" last="Peeling">James Peeling</name></country><country name="Japon"><noRegion><name sortKey="Imai, Yumi" sort="Imai, Yumi" uniqKey="Imai Y" first="Yumi" last="Imai">Yumi Imai</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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