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    Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve transection

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    Access Status
    Open access
    Authors
    Toomey, L.
    Bartlett, C.
    Majimbi, Maimuna
    Gopalasingam, G.
    Rodger, J.
    Fitzgerald, Melinda
    Date
    2018
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Toomey, L. and Bartlett, C. and Majimbi, M. and Gopalasingam, G. and Rodger, J. and Fitzgerald, M. 2018. Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve transection. Experimental Brain Research. 237 (1): pp, 161-171.
    Source Title
    Experimental Brain Research
    DOI
    10.1007/s00221-018-5414-0
    ISSN
    0014-4819
    School
    Health Sciences Research and Graduate Studies
    Remarks

    The final publication is available at Springer via http://dx.doi.org/10.1007/s00221-018-5414-0

    URI
    http://hdl.handle.net/20.500.11937/73203
    Collection
    • Curtin Research Publications
    Abstract

    Following neurotrauma, secondary degeneration of neurons and glia adjacent to the injury leads to further functional loss. A combination of ion channel inhibitors (lomerizine + oxATP + YM872) has been shown to be effective at limiting structural and functional loss due to secondary degeneration. Here we assess efficacy of the combination where oxATP is replaced with Brilliant Blue G (BBG), a more clinically applicable P2X7 receptor inhibitor. Partial optic nerve transection was used to model secondary degeneration in adult female rats. Animals were treated with combinations of lomerizine + YM872 + oxATP or lomerizine + YM872 + BBG, delivered via osmotic mini-pump directly to the injury site. Outcomes assessed were Iba1 + and ED1 + microglia and macrophages, oligodendroglial cell numbers, node/paranode structure and visual function using the optokinetic nystagmus test. The lomerizine + BBG + YM872 combination was at least as effective at the tested concentrations as the lomerizine + oxATP + YM872 combination at preserving node/paranode structure and visual function when delivered locally. However, neither ion channel inhibitor combination significantly improved microglial/macrophage nor oligodendroglial numbers compared to vehicle-treated controls. In conclusion, a locally delivered combination of ion channel inhibitors incorporating lomerizine + BBG + YM872 is at least as effective at limiting secondary degeneration following partial injury to the optic nerve as the combination incorporating oxATP.

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