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

Research output: Contribution to journalArticle

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

Cite this

Toomey, Lillian M. ; Bartlett, Carole A. ; Majimbi, Maimuna ; Gopalasingam, Gopana ; Rodger, Jennifer ; Fitzgerald, Melinda. / Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve transection. In: Experimental Brain Research. 2019 ; Vol. 237, No. 1. pp. 161-171.
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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.",
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Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve transection. / Toomey, Lillian M.; Bartlett, Carole A.; Majimbi, Maimuna; Gopalasingam, Gopana; Rodger, Jennifer; Fitzgerald, Melinda.

In: Experimental Brain Research, Vol. 237, No. 1, 01.2019, p. 161-171.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve transection

AU - Toomey, Lillian M.

AU - Bartlett, Carole A.

AU - Majimbi, Maimuna

AU - Gopalasingam, Gopana

AU - Rodger, Jennifer

AU - Fitzgerald, Melinda

PY - 2019/1

Y1 - 2019/1

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AB - 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.

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KW - Ion channel inhibitor

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KW - Visual function

KW - RETINAL GANGLION-CELLS

KW - TRAUMATIC BRAIN-INJURY

KW - BRILLIANT BLUE G

KW - MYELIN

KW - CALPAIN

KW - DAMAGE

KW - MODEL

KW - OLIGODENDROCYTES

KW - DEMYELINATION

KW - DISRUPTION

U2 - 10.1007/s00221-018-5414-0

DO - 10.1007/s00221-018-5414-0

M3 - Article

VL - 237

SP - 161

EP - 171

JO - Experimental Brain Research

JF - Experimental Brain Research

SN - 0014-4819

IS - 1

ER -