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

NEUROPHARMACOLOGY

卷:63

Article

Bei, Fengfeng¹  Smith, Kenneth J.¹ 

[1] UCL, Inst Neurol, Dept Neuroinflammat, London WC1N 1PJ, England

关键词: Ischemia;    Stroke;    White matter injury;    Axonal protection;    Sodium/calcium exchanger;   

DOI  :  10.1016/j.neuropharm.2012.04.019

来源: Elsevier

【 摘 要 】

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 = 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. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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