Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice
Identifieur interne : 002E44 ( Main/Exploration ); précédent : 002E43; suivant : 002E45Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice
Auteurs : Jennifer E. A. Wells [Canada] ; R. John Hurlbert [Canada] ; Michael G. Fehlings [Canada] ; V. Wee Yong [Canada]Source :
- Brain [ 0006-8950 ] ; 2003-07.
English descriptors
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Abstract
Acute spinal cord injury (SCI) produces tissue damage that continues to evolve days and weeks after the initial insult, with corresponding functional impairments. Reducing the extent of progressive tissue loss (‘neuroprotection’) following SCI should result in a better recovery from SCI, but treatment options have thus far been limited. In this study, we have tested the efficacy of minocycline in ameliorating damage following acute SCI in mice. This semi‐synthetic tetracycline antibiotic has been reported to inhibit the expression and activity of several mediators of tissue injury, including inflammatory cytokines, free radicals and matrix metalloproteinases, making it a suitable candidate for study. Mice were subjected to extradural compression of the spinal cord using a modified aneurysm clip, following which they received treatment with either minocycline or vehicle beginning 1 h after injury. Behavioural testing of hindlimb function was initiated 3 days after injury using the Basso Beattie Bresnahan locomotor rating scale, and at 1 week using the inclined plane test. Functional assessments demonstrated that minocycline administration significantly improved both hindlimb function and strength from 3 to 28 days after injury compared with vehicle controls. Furthermore, gross lesion size in the spinal cord was significantly reduced by minocycline, and there was evidence of axonal sparing as determined using fluorogold labelling of the rubrospinal tract and by Bielchowsky silver stain. Finally, a comparison of minocycline against the currently approved treatment for acute SCI in humans, methylprednisolone, demonstrated superior behavioural recovery in the minocycline‐treated animals.
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DOI: 10.1093/brain/awg178
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A." last="Wells">Jennifer E. A. Wells</name><affiliation wicri:level="4"><orgName type="university">Université de Calgary</orgName><country>Canada</country><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author><author><name sortKey="Hurlbert, R John" sort="Hurlbert, R John" uniqKey="Hurlbert R" first="R. John" last="Hurlbert">R. John Hurlbert</name><affiliation wicri:level="4"><orgName type="university">Université de Calgary</orgName><country>Canada</country><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author><author><name sortKey="Fehlings, Michael G" sort="Fehlings, Michael G" uniqKey="Fehlings M" first="Michael G." last="Fehlings">Michael G. Fehlings</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurosurgery, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Yong, V Wee" sort="Yong, V Wee" uniqKey="Yong V" first="V. Wee" last="Yong">V. Wee Yong</name><affiliation wicri:level="4"><orgName type="university">Université de Calgary</orgName><country>Canada</country><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><title level="j" type="abbrev">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2003-07">2003-07</date><biblScope unit="volume">126</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="1628">1628</biblScope><biblScope unit="page" to="1637">1637</biblScope></imprint><idno type="ISSN">0006-8950</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abbreviations: MMP = matrix metalloproteinase; NO = nitric oxide; SCI = spinal cord injury</term><term>Keywords: inflammation; minocycline; neuroprotection; recovery; spinal cord injury</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Acute spinal cord injury (SCI) produces tissue damage that continues to evolve days and weeks after the initial insult, with corresponding functional impairments. Reducing the extent of progressive tissue loss (‘neuroprotection’) following SCI should result in a better recovery from SCI, but treatment options have thus far been limited. In this study, we have tested the efficacy of minocycline in ameliorating damage following acute SCI in mice. This semi‐synthetic tetracycline antibiotic has been reported to inhibit the expression and activity of several mediators of tissue injury, including inflammatory cytokines, free radicals and matrix metalloproteinases, making it a suitable candidate for study. Mice were subjected to extradural compression of the spinal cord using a modified aneurysm clip, following which they received treatment with either minocycline or vehicle beginning 1 h after injury. Behavioural testing of hindlimb function was initiated 3 days after injury using the Basso Beattie Bresnahan locomotor rating scale, and at 1 week using the inclined plane test. Functional assessments demonstrated that minocycline administration significantly improved both hindlimb function and strength from 3 to 28 days after injury compared with vehicle controls. Furthermore, gross lesion size in the spinal cord was significantly reduced by minocycline, and there was evidence of axonal sparing as determined using fluorogold labelling of the rubrospinal tract and by Bielchowsky silver stain. Finally, a comparison of minocycline against the currently approved treatment for acute SCI in humans, methylprednisolone, demonstrated superior behavioural recovery in the minocycline‐treated animals.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Alberta</li><li>Ontario</li></region><settlement><li>Calgary</li><li>Toronto</li></settlement><orgName><li>Université de Calgary</li><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Alberta"><name sortKey="Wells, Jennifer E A" sort="Wells, Jennifer E A" uniqKey="Wells J" first="Jennifer E. A." last="Wells">Jennifer E. A. Wells</name></region><name sortKey="Fehlings, Michael G" sort="Fehlings, Michael G" uniqKey="Fehlings M" first="Michael G." last="Fehlings">Michael G. Fehlings</name><name sortKey="Hurlbert, R John" sort="Hurlbert, R John" uniqKey="Hurlbert R" first="R. John" last="Hurlbert">R. John Hurlbert</name><name sortKey="Yong, V Wee" sort="Yong, V Wee" uniqKey="Yong V" first="V. Wee" last="Yong">V. Wee Yong</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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