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Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery. We analyzed minocycline's neuroprotective effects over 28\u2003days following contusion SCI and found significant functional recovery compared to tetracycline. Histology, immunocytochemistry, and image analysis indicated statistically significant tissue sparing, reduced apoptosis and microgliosis, and less activated caspase\u20103 and substrate cleavage. Since our original report in abstract form, others have published both positive and negative effects of minocycline in various rodent models of SCI and with various routes of administration. We have since found decreased tumor necrosis factor\u2010\u03b1, as well as caspase\u20103 mRNA expression, as possible mechanisms of action for minocycline's ameliorative action. These results support reports that modulating apoptosis, caspases, and microglia provide promising therapeutic targets for prevention and\/or limiting the degree of functional loss after CNS trauma. Minocycline, and more potent chemically synthesized tetracyclines, may find a place in the therapeutic arsenal to promote recovery early after SCI in humans.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.03799.x","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T16:34:56Z","timestamp":1145637296000},"page":"1314-1326","source":"Crossref","is-referenced-by-count":202,"title":["Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury"],"prefix":"10.1111","volume":"97","author":[{"given":"Barry W.","family":"Festoff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Ameenuddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S.","family":"Santacruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Citron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1523\/JNEUROSCI.17-03-01055.1997","article-title":"Role of NMDA and non\u2010NMDA ionotropic glutamate receptors in traumatic spinal cord axonal injury","volume":"17","author":"Agrawal S. 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