• Neuroscience · Aug 2016

    Investigation of the mechanisms of neuroprotection mediated by Ro5-4864 in brain injury.

    • Eilam Palzur, Aviram Sharon, Mona Shehadeh, and Jean Francois Soustiel.
    • Eliachar Research Laboratory, Medical Center of the Galilee, Faculty of Medicine in the Galilee, University of Bar Ilan, Naharia 22100, Israel.
    • Neuroscience. 2016 Aug 4; 329: 162-70.

    AbstractIncreasing evidence has established the involvement of the 18-kDa translocator protein (TSPO) in the process of mitochondrial membrane permeabilization and subsequent apoptosis through modulation of the mitochondrial permeability transition pore. Recent studies have shown that treatment with Ro5-4864, a TSPO ligand, resulted in a neuroprotective effect in traumatic brain injury. Yet, the nature of this effect remained uncertain as mature neurons are considered to be lacking the TSPO protein. In order to investigate the mechanism of Ro5-4864-mediated neuroprotection, the neuro-inflammatory and neurosteroid response to cortical injury was tested in sham-operated, vehicle, cyclosporine A (CsA) and Ro5-4864-treated rats. As anticipated, the levels of interleukin 1β and tumor necrosis factor α, as well as the astrocyte and microglia cellular density in the injured area were all decreased by CsA in comparison with the vehicle group. By contrast, no visible effect could be observed in Ro5-4864-treated animals. None of the groups showed any significant difference with any other in respect with the expression of brain-derived neurotrophic factor. Double immunofluorescence staining with NeuN and TSPO confirmed the absence of TSPO in native neurons though showed clear evidence of co-localization of TSPO in the cytoplasm of NeuN-stained injured neurons. Altogether, this study shows that the neuronal protection mediated by Ro5-4864 in brain injury cannot be solely attributed to an indirect effect of the ligand on glial TSPO but may also represent the consequence of the modulation of upregulated TSPO in injured neurons. This observation may be of importance for future pharmacological research in neurotrauma.Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…