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Axonal protection achieved by blockade of sodium/calcium exchange in a new model of ischemia in vivo.

Bei, F; Smith, KJ; (2012) Axonal protection achieved by blockade of sodium/calcium exchange in a new model of ischemia in vivo. Neuropharmacology , 63 (3) 405 - 414. 10.1016/j.neuropharm.2012.04.019. Green open access

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Abstract

Ischemic white matter injury has been relatively little studied despite its importance to the outcome of stroke. To aid such research a new rat model has been developed in vivo and used to assess whether blockade of the sodium/calcium exchanger is effective in protecting central axons from ischemic injury. Vasoconstrictive agent endothelin-1 was injected into the rat spinal cord to induce ischemia. KB-R7943 or SEA0400 was administered systemically to block the operation of the sodium/calcium exchanger. Endothelin-1 caused profound reduction of local blood perfusion and resulted in a prompt loss of axonal conduction. Whereas recovery of conduction following vehicle administration was only to 10.5 ± 9% of baseline (n = 8) 4.5 h after endothelin-1 injection, recovery following KB-R7943 (30 mg/kg, i.a.) administration was increased to 35 ± 9% of baseline (n = 6; P < 0.001). SEA0400 (30 mg/kg, i.a.) was also protective (33.2 ± 6% of baseline, n = 4; P < 0.001). Neither drug improved conduction by diminishing the severity of the ischemia. The protective effect of KB-R7943 persisted for at least 3 days after ischemia, as it improved axonal conduction (76.3 ± 11% for KB-R7943 vs. 51.0 ± 19% for vehicle; P < 0.01) and reduced lesion area (55.6 ± 15% for KB-R7943 vs. 77.9 ± 9% for vehicle; P < 0.01) at this time. In conclusion, a new model of white matter ischemia has been introduced suitable for both structural and functional studies in vivo. Blocking the sodium/calcium exchanger protects central axons from ischemic injury in vivo.

Type: Article
Title: Axonal protection achieved by blockade of sodium/calcium exchange in a new model of ischemia in vivo.
Location: UK
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuropharm.2012.04.019
Publisher version: http://dx.doi.org/10.1016/j.neuropharm.2012.04.019
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3657694
Keywords: Aniline Compounds, Animals, Axons, Brain, Brain Ischemia, Electrophysiological Phenomena, Endothelin-1, Immunohistochemistry, Neural Conduction, Neuroprotective Agents, Phenyl Ethers, Rats, Rats, Sprague-Dawley, Sodium-Calcium Exchanger, Thiourea
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1349311
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