کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5999400 | 1181485 | 2011 | 9 صفحه PDF | دانلود رایگان |
ObjectiveThe study investigated a possible neuroprotective potency of minocycline in an experimental asphyxial cardiac arrest (ACA) rat model. Clinically important survival times were evaluated thus broadening common experimental approaches.MethodsAdult rats were subjected to 5Â min of ACA followed by resuscitation. There were two main treatment groups: ACA and sham operated. Relating to minocycline treatment each group consisted of three sub-groups: pre-, post-, and sans-mino, with three different survival times: 4, 7, and 21 days. Neurodegeneration and microgliosis were monitored by immunohistochemistry. Alterations of microglia-associated gene expression were analyzed by quantitative RT-PCR.ResultsACA induced massive nerve cell loss and activation of microglia/macrophages in hippocampal CA1 cell layer intensifying with survival time. After 7 days, minocycline significantly decreased both, neuronal degeneration and microglia response in dependence on the application pattern; application post ACA was most effective. After 21 days, neuroprotective effects of minocycline were lost. ACA significantly induced expression of the microglia-associated factors Ccl2, CD45, Mac-1, F4-80, and Tnfa. Independent on survival time, minocycline affected these parameters not significantly. Expression of iNOS was unaffected by both, ACA and minocycline.ConclusionsIn adult rat hippocampus microglia was significantly activated by ACA. Minocycline positive affected neuronal survival and microglial response temporary, even when applied up to 18Â h after ACA, thus defining a therapeutically-relevant time window. As ACA-induced neuronal cell death involves acute and delayed events, longer minocycline intervention targeting also secondary injury cascades should manifest neuroprotective potency, a question to be answered by further experiments.
Journal: Resuscitation - Volume 82, Issue 3, March 2011, Pages 341-349