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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 language | English |
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Pages (from-to) | 161-171 |
Number of pages | 11 |
Journal | Experimental Brain Research |
Volume | 237 |
Issue number | 1 |
DOIs | |
Publication status | Published - 31 Jan 2019 |
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Dive into the research topics of 'Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve transection'. Together they form a unique fingerprint.Projects
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Innovative and multi-disciplinary treatment strategies for secondary degeneration following neurotrauma
Fitzgerald, M. (Investigator 01)
NHMRC National Health and Medical Research Council
1/01/15 → 30/12/18
Project: Research