Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury

James J Donkin; A J Nimmo; I Cernak; P C Blumbergs; R Vink

doi:10.1038/jcbfm.2009.63

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Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury

Journal article

Peer reviewed

Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury

James J Donkin, A J Nimmo, I Cernak, P C Blumbergs and R Vink

Journal of Cerebral Blood Flow and Metabolism, Vol.29(8), pp.1388-1398

2009

DOI: https://doi.org/10.1038/jcbfm.2009.63

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Abstract

brain trauma

cerebral edema

neurogenic inflammation

neuropeptides

Brain edema and swelling is a critical factor in the high mortality and morbidity associated with traumatic brain injury (TBI). Despite this, the mechanisms associated with its development are poorly understood and interventions have not changed in over 30 years. Although neuropeptides and neurogenic inflammation have been implicated in peripheral edema formation, their role in the development of central nervous system edema after brain trauma has not been investigated. This study examines the role of the neuropeptide, substance P (SP), in the development of edema and functional deficits after brain trauma in rats. After severe diffuse TBI in adult male rats, neuronal and perivascular SP immunoreactivity were increased markedly. Perivascular SP colocalized with exogenously administered Evans blue, supporting a role for SP in vascular permeability. Inhibition of SP action by administration of the neurokinin-1 (NK 1) antagonist, N-acetyl-L-tryptophan, at 30 mins after trauma attenuated vascular permeability and edema formation. Administration of the NK 1 antagonist also improved both motor and cognitive neurologic outcomes. These findings suggest that SP release is integrally linked to the increased vascular permeability and edema formation after brain trauma, and that treatment with an NK 1 receptor antagonist reduces edema and improves neurologic outcome. © 2009 ISCBFM.

Details

Title: Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury
Authors: James J Donkin (Author) - University of Adelaide
A J Nimmo (Author) - University of Adelaide
I Cernak (Author) - Johns Hopkins University, United States
P C Blumbergs (Author) - Hanson Institute Centre for Neurological Diseases
R Vink (Author) - University of Adelaide
Publication details: Journal of Cerebral Blood Flow and Metabolism, Vol.29(8), pp.1388-1398
Publisher: Sage Publications Ltd.
Date published: 2009
DOI: 10.1038/jcbfm.2009.63
ISSN: 0271-678X
Organisation Unit: UniSC Clinical Trials Centre; University of the Sunshine Coast, Queensland
Language: English
Record Identifier: 99451056302621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Endocrinology & Metabolism; Hematology; Neurosciences

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