Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection
© 2019, The Author(s). Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in...
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| Format: | Journal Article |
| Language: | English |
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NATURE RESEARCH
2019
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| Online Access: | http://purl.org/au-research/grants/nhmrc/1087114 http://hdl.handle.net/20.500.11937/81498 |
| _version_ | 1848764378796523520 |
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| author | Toomey, Lilian Bartlett, C.A. Gavriel, N. McGonigle, Terence Majimbi, Maimuna Gopalasingam, G. Rodger, J. Fitzgerald, Melinda |
| author_facet | Toomey, Lilian Bartlett, C.A. Gavriel, N. McGonigle, Terence Majimbi, Maimuna Gopalasingam, G. Rodger, J. Fitzgerald, Melinda |
| author_sort | Toomey, Lilian |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2019, The Author(s).
Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X7 receptors and Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma. |
| first_indexed | 2025-11-14T11:18:25Z |
| format | Journal Article |
| id | curtin-20.500.11937-81498 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:18:25Z |
| publishDate | 2019 |
| publisher | NATURE RESEARCH |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-814982020-11-03T06:35:18Z Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection Toomey, Lilian Bartlett, C.A. Gavriel, N. McGonigle, Terence Majimbi, Maimuna Gopalasingam, G. Rodger, J. Fitzgerald, Melinda Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics BRAIN-BARRIER PERMEABILITY RETINAL GANGLION-CELLS RECEPTOR ANTAGONIST OXIDATIVE STRESS P2X7 RECEPTORS CEREBRAL EDEMA DRUG-DELIVERY CA2+ INFLUX HEAD-INJURY DAMAGE © 2019, The Author(s). Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X7 receptors and Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma. 2019 Journal Article http://hdl.handle.net/20.500.11937/81498 10.1038/s41598-019-51886-3 English http://purl.org/au-research/grants/nhmrc/1087114 http://creativecommons.org/licenses/by/4.0/ NATURE RESEARCH fulltext |
| spellingShingle | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics BRAIN-BARRIER PERMEABILITY RETINAL GANGLION-CELLS RECEPTOR ANTAGONIST OXIDATIVE STRESS P2X7 RECEPTORS CEREBRAL EDEMA DRUG-DELIVERY CA2+ INFLUX HEAD-INJURY DAMAGE Toomey, Lilian Bartlett, C.A. Gavriel, N. McGonigle, Terence Majimbi, Maimuna Gopalasingam, G. Rodger, J. Fitzgerald, Melinda Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection |
| title | Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection |
| title_full | Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection |
| title_fullStr | Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection |
| title_full_unstemmed | Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection |
| title_short | Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection |
| title_sort | comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection |
| topic | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics BRAIN-BARRIER PERMEABILITY RETINAL GANGLION-CELLS RECEPTOR ANTAGONIST OXIDATIVE STRESS P2X7 RECEPTORS CEREBRAL EDEMA DRUG-DELIVERY CA2+ INFLUX HEAD-INJURY DAMAGE |
| url | http://purl.org/au-research/grants/nhmrc/1087114 http://hdl.handle.net/20.500.11937/81498 |