Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/89677
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dc.contributor.authorHarford-Wright, E.en
dc.contributor.authorLewis, K.en
dc.contributor.authorGhabriel, M.en
dc.contributor.authorVink, R.en
dc.date.issued2014en
dc.identifier.citationPLoS One, 2014; 9(5):e97002-1-e97002-7en
dc.identifier.issn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/2440/89677-
dc.description.abstractThe neuropeptide substance P (SP) has been implicated in the disruption of the blood-brain barrier (BBB) and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg), dexamethasone (8 mg/kg) or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05). Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants further investigation as a potential anti-edematous treatment.en
dc.description.statementofresponsibilityElizabeth Harford-Wright, Kate M. Lewis, Mounir N. Ghabriel, Robert Vinken
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2014 Harford-Wright et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectBlood-Brain Barrier; Animals; Humans; Mice; Brain Neoplasms; Brain Edema; Disease Models, Animal; Morpholines; Substance P; Receptors, Neurokinin-1; Permeability; Male; Neurokinin-1 Receptor Antagonistsen
dc.titleTreatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumorsen
dc.typeJournal articleen
dc.identifier.rmid0030010509en
dc.identifier.doi10.1371/journal.pone.0097002en
dc.identifier.pubid113994-
pubs.library.collectionMedical Sciences publicationsen
pubs.library.teamDS08en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidGhabriel, M. [0000-0002-9153-271X]en
dc.identifier.orcidVink, R. [0000-0002-4885-0667]en
Appears in Collections:Medical Sciences publications

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