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 Fitzgerald

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3 Citations (Scopus)
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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 P2X(7) 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.

Original languageEnglish
Pages (from-to)161-171
Number of pages11
JournalExperimental Brain Research
Volume237
Issue number1
DOIs
Publication statusPublished - Jan 2019

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