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https://hdl.handle.net/2440/67168
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Type: | Journal article |
Title: | A substance P antagonist improves outcome when administered 4 h after onset of ischaemic stroke |
Author: | Turner, R. Helps, S. Thornton, E. Vink, R. |
Citation: | Brain Research, 2011; 1393:84-90 |
Publisher: | Elsevier Science Bv |
Issue Date: | 2011 |
ISSN: | 0006-8993 1872-6240 |
Statement of Responsibility: | Renée J. Turner, Stephen C. Helps, Emma Thornton and Robert Vink |
Abstract: | Previous studies have suggested that substance P (SP) plays a critical role in the development of brain oedema and functional deficits following traumatic brain injury and that SP receptor antagonism may improve outcome. No studies have described such a role in ischemic stroke. The present study characterized the effects of the NK1 tachykinin receptor antagonist, n-acetyl-L-tryptophan (NAT), on blood-brain barrier (BBB) breakdown, oedema formation, infarct volume and functional outcome following reversible ischemic stroke in rats. Ischemia was induced using a reversible thread model of middle cerebral artery occlusion where occlusion was maintained for 2 h before reperfusion. Animals received either NAT or equal volume saline vehicle intravenously at 2 h post-reperfusion. Ischaemic stroke resulted in increased perivascular SP immunoreactivity at 24 h. Administration of NAT significantly reduced oedema formation and BBB permeability at 24 h post-ischemia and significantly improved functional outcome as assessed over 7 days. There was no effect on infarct volume. We conclude that inhibition of SP activity with a NK1 tachykinin receptor antagonist is effective in reducing cerebral oedema, BBB permeability and functional deficits following reversible ischemia and may therefore represent a novel therapeutic approach to the treatment of ischaemic stroke. |
Keywords: | Ischaemic stroke NK1 tachykinin receptor antagonist Oedema Neuropeptides Neurogenic inflammation |
Rights: | © 2011 Elsevier B.V. All rights reserved. |
DOI: | 10.1016/j.brainres.2011.03.066 |
Published version: | http://dx.doi.org/10.1016/j.brainres.2011.03.066 |
Appears in Collections: | Aurora harvest 5 Medical Sciences publications |
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