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Experimental Brain Research

, Volume 237, Issue 1, pp 161–171 | Cite as

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

  • Lillian M. Toomey
  • Carole A. Bartlett
  • Maimuna Majimbi
  • Gopana Gopalasingam
  • Jennifer Rodger
  • Melinda FitzgeraldEmail author
Research Article

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.

Keywords

Secondary degeneration Neurotrauma Ion channel inhibitor Myelin Visual function 

Notes

Acknowledgements

MF is supported by an NHMRC Career Development Fellowship (APP1087114).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Experimental and Regenerative Neurosciences, School of Biological SciencesThe University of Western AustraliaPerthAustralia
  2. 2.Curtin Health Innovation Research InstituteCurtin UniversityBentleyAustralia
  3. 3.Perron Institute for Neurological and Translational ScienceSarich Neuroscience Research Institute BuildingNedlandsAustralia

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