title: Substance P antagonists as a novel intervention for brain edema and raised intracranial pressure.
abstract: Increased intracranial pressure (ICP) following acute brain injury requires the accumulation of additional water in the intracranial vault. One source of such water is the vasculature, although the mechanisms associated with control of blood-brain barrier permeability are unclear. We have recently shown that acute brain injury, such as neurotrauma and stroke, results in perivascular accumulation of the neuropeptide, substance P. This accumulation is associated with increased blood-brain barrier permeability and formation of vasogenic edema. Administration of a substance P antagonist targeting the tachykinin NK1 receptor profoundly reduced the increased blood-brain barrier permeability and edema formation, and in small animal models of acute brain injury, improved functional outcome. In a large, ovine model of experimental traumatic brain injury, trauma resulted in a significant increase in ICP. Administration of an NK1 antagonist caused a profound reduction in post--traumatic ICP, with levels returning to normal within 4 h of drug administration. Substance P NK1 antagonists offer a novel therapeutic approach to the treatment of acute brain injury.
authors.affiliation: School of Medical Sciences, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Levon
authors.initials: L
authors.lastname: Gabrielian
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Helps
authors.forename: Emma
authors.initials: E
authors.lastname: Thornton
authors.forename: Renée J
authors.initials: RJ
authors.lastname: Turner
authors.forename: Anna V
authors.initials: AV
authors.lastname: Leonard
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D001930:Brain Injuries / Q000150:complications; D004195:Disease Models, Animal; D006801:Humans; D019586:Intracranial Hypertension / Q000209:etiology*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018039:Receptors, Tachykinin; D013373:Substance P