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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
Statement of
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.
RMID: 0020109421
DOI: 10.1016/j.brainres.2011.03.066
Appears in Collections:Medical Sciences publications

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