Source:http://linkedlifedata.com/resource/pubmed/id/15453986
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2004-9-29
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pubmed:abstractText |
Pre- and post-injury Cyclosporin A (CsA) administration has shown neuroprotective properties by ameliorating mitochondrial damage. The aim of this study was to assess the effect of CsA upon N-acetylaspartate (NAA) reduction and ATP loss, two sensitive markers of mitochondrial dysfunction and bioenergetic impairment. Adult male Sprague-Dawley rats were exposed to impact acceleration traumatic brain injury (2 m/450 g) and randomized into the following experimental groups: intrathecal CsA/vehicle treated (n = 12), intravenous CsA/vehicle treated (n = 18) and sham (n = 12). Intrathecal treatment consisted of post-injury (30 min) cisternal bolus of CsA or Vehicle (0.15 mL, 10 mg/kg). Intravenous administration consisted of 30 min post-injury continuous 1 hour infusion of either 20 or 35 mg/kg CsA or Vehicle. Quantitative HPLC analysis of whole brain samples was performed 6 h post-injury for levels of NAA and ATP. Following intrathecal delivery CsA demonstrated significant neuroprotection blunting a 30% NAA reduction (p < 0.001) and restoring 26% of the ATP loss (p < 0.005). The 20 mg/kg intravenous dose failed to ameliorate the biochemical damages while the 35 mg/kg dosage showed 36% NAA recovery and 39% ATP restoration (p < 0.001). In conclusion, CsA is capable of restoring ATP and blunting NAA reduction. Intravenous infusion of 35 mg/kg appears to be the optimal therapeutic strategy in this model. These findings contribute to the notion that CsA achieves neuroprotection, preserving mitochondrial function, and provides a rationale for the assessment of CsA in the clinical setting where MR spectroscopy can monitor NAA and ATP in brain-injured patients.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0897-7151
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1154-67
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15453986-Animals,
pubmed-meshheading:15453986-Aspartic Acid,
pubmed-meshheading:15453986-Brain Injuries,
pubmed-meshheading:15453986-Cyclosporine,
pubmed-meshheading:15453986-Drug Administration Schedule,
pubmed-meshheading:15453986-Infusions, Intravenous,
pubmed-meshheading:15453986-Injections, Spinal,
pubmed-meshheading:15453986-Male,
pubmed-meshheading:15453986-Mitochondria,
pubmed-meshheading:15453986-Neuroprotective Agents,
pubmed-meshheading:15453986-Rats,
pubmed-meshheading:15453986-Rats, Sprague-Dawley
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pubmed:year |
2004
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pubmed:articleTitle |
The protective effect of cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury.
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pubmed:affiliation |
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0508, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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