Journal of Neuroinflammation | |
Neuregulin-1 inhibits neuroinflammatory responses in a rat model of organophosphate-nerve agent-induced delayed neuronal injury | |
Byron D Ford5  Monique C Surles-Zeigler5  Timothy J Distel5  Alicia S Gates5  Teclemichael Tewolde5  Donald A Bruun1  Todd E White5  Kyndra C Stovall3  Cuimei Liu4  Gregory D Ford2  Pamela J Lein1  Yonggang Li5  | |
[1] Department of Molecular Biosciences, School of Veterinary Medicine, University of California, 1089 Veterinary Medicine Drive, Davis 95616, CA, USA;Department of Biology, Morehouse College, 830 Westview Drive SW, Atlanta 30310, GA, USA;Department of Physiology, Emory University, 201 Dowman Dr., Atlanta 30322, GA, USA;Institute of Infectious Disease, Xiangya Hospital, Central-South University, No.9 Chegongzhuang Avenue, Changsha 100044, China;Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, 720 Westview Drive, SW, Atlanta 30310, GA, USA | |
关键词: Rat model; Nerve agent; Neuroprotection; Microarray; Immunity; Delayed neurotoxicity; Cytokine; Chemokine; Apoptosis; | |
Others : 1227101 DOI : 10.1186/s12974-015-0283-y |
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received in 2014-12-19, accepted in 2015-03-17, 发布年份 2015 | |
【 摘 要 】
Background
Neuregulin-1 (NRG-1) has been shown to act as a neuroprotectant in animal models of nerve agent intoxication and other acute brain injuries. We recently demonstrated that NRG-1 blocked delayed neuronal death in rats intoxicated with the organophosphate (OP) neurotoxin diisopropylflurophosphate (DFP). It has been proposed that inflammatory mediators are involved in the pathogenesis of OP neurotoxin-mediated brain damage.
Methods
We examined the influence of NRG-1 on inflammatory responses in the rat brain following DFP intoxication. Microglial activation was determined by immunohistchemistry using anti-CD11b and anti-ED1 antibodies. Gene expression profiling was performed with brain tissues using Affymetrix gene arrays and analyzed using the Ingenuity Pathway Analysis software. Cytokine mRNA levels following DFP and NRG-1 treatment was validated by real-time reverse transcription polymerase chain reaction (RT-PCR).
Results
DFP administration resulted in microglial activation in multiple brain regions, and this response was suppressed by treatment with NRG-1. Using microarray gene expression profiling, we observed that DFP increased mRNA levels of approximately 1,300 genes in the hippocampus 24 h after administration. NRG-1 treatment suppressed by 50% or more a small fraction of DFP-induced genes, which were primarily associated with inflammatory responses. Real-time RT-PCR confirmed that the mRNAs for pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly increased following DFP exposure and that NRG-1 significantly attenuated this transcriptional response. In contrast, tumor necrosis factor α (TNFα) transcript levels were unchanged in both DFP and DFP + NRG-1 treated brains relative to controls.
Conclusion
Neuroprotection by NRG-1 against OP neurotoxicity is associated with the suppression of pro-inflammatory responses in brain microglia. These findings provide new insight regarding the molecular mechanisms involved in the neuroprotective role of NRG-1 in acute brain injuries.
【 授权许可】
2015 Li et al.; licensee BioMed Central.
【 预 览 】
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