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Please use this identifier to cite or link to this item:
https://ir.csmu.edu.tw:8080/ir/handle/310902500/3795
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Title: | Melatonin inhibits microglial activation, reduces pro-inflammatory cytokine levels, and rescues hippocampal neurons of adult rats with acute Klebsiella pneumoniae meningitis |
Authors: | Un-In Wu;Fu-Der Mai;Ji-Nan Sheu;Li-You Chen;Yu-Ting Liu;Hai-Cheng Huang;Hung-Ming Chang |
Contributors: | 中山醫學大學:醫學系 |
Keywords: | apoptosis;bacterial meningitis;interleukins;melatonin;microglia;quantitative molecular imaging analysis;tumor necrosis factor- |
Date: | 2010 |
Issue Date: | 2011-05-20T08:45:09Z (UTC)
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ISSN: | 0742-3098 |
Abstract: | Acute bacterial meningitis caused by Klebsiella pneumoniae (K. pneumoniae) is a major health threat with a high mortality rate and severe neuro-cognitive sequelae. The intense pro-inflammatory cytokine released from calcium-mediated microglial activation plays an important role in eliciting neuronal damage in the hippocampal region. Considering melatonin possesses anti-inflammatory and immuno-modulatory properties, the present study determined whether melatonin can effectively decrease inflammatory responses and prevent hippocampal damage in animals subjected to K. pneumoniae. Adult rats inoculated with K. pneumoniae received a melatonin injection immediately thereafter at doses of 5, 25, 50, or 100 mg/kg. Following 24 h of survival, all experimental animals were processed for time-of-flight secondary ion mass spectrometry (for detecting glial calcium intensity), isolectin-B4 histochemistry (reliable marker for microglial activation), pro-inflammatory cytokine measurement as well as cytochrome oxidase and in situ dUTP end-labeling (representing neuronal bio-energetic status and apoptotic changes, respectively). Results indicate that in K. pneumoniae-infected rats, numerous calcium-enriched microglia, enhanced pro-inflammatory cytokine, and various apoptotic neurons with low bio-energetic activity were detected in hippocampus. Following melatonin administration, however, all parameters including glial calcium intensity, microglial activation, pro-inflammatory cytokine levels, and number of apoptotic neurons were successfully decreased with maximal change observed at a melatonin dose of 100 mg/kg. Enzymatic data corresponded well with above findings in which all surviving neurons displayed high bio-energetic activity. As effectively reducing glia-mediated inflammatory response is neuro-protective to hippocampal neurons, the present study supports the clinical use of melatonin as a potential therapeutic agent to counteract K. pneumoniae meningitis-induced neuro-cognitive damage. |
URI: | https://ir.csmu.edu.tw:8080/handle/310902500/3795 http://dx.doi.org/10.1111/j.1600-079X.2010.00825.x |
Relation: | Journal of Pineal Research,Volume 50, Issue 2, pages 159–170, March 2011 |
Appears in Collections: | [醫學系] 期刊論文
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