Substance P Antagonists As a Therapeutic Approach to Improving Outcome Following Traumatic Brain Injury

Overview

Journal Neurotherapeutics

Specialty Neurology

Date 2010 Feb 5

PMID 20129499

Citations 20

Authors

Robert Vink

Corinna Van Den Heuvel

Affiliations

Soon will be listed here.

Abstract

Although a number of secondary injury factors are known to contribute to the development of morphological injury and functional deficits following traumatic brain injury, accumulating evidence has suggested that neuropeptides, and in particular substance P, may play a critical role. Substance P is released early following acute injury to the CNS as part of a neurogenic inflammatory response. In so doing, it facilitates an increase in the permeability of the blood-brain barrier and the development of vasogenic edema. At the cellular level, substance P has been shown to directly result in neuronal cell death; functionally, substance P has been implicated in learning and memory, mood and anxiety, stress mechanisms, emotion-processing, migraine, emesis, pain, and seizures, all of which may be adversely affected after brain injury. Inhibition of post-traumatic substance P activity, either by preventing release or by antagonism of the neurokinin-1 receptor, has consistently resulted in a profound decrease in development of edema and marked improvements in functional outcome. This review summarizes the current evidence supporting a role for substance P in acute brain injury.

Citing Articles

Onabotulinumtoxin A for the Treatment of Post-Traumatic Headache: Is It Better than Anti-CGRP Antibodies?.

Pellesi L, Onan D, Martelletti P Toxins (Basel). 2024; 16(10).

PMID: 39453203 PMC: 11510946. DOI: 10.3390/toxins16100427.

NK1 tachykinin receptor antagonist treatment reduces cerebral edema and intracranial pressure in an ovine model of ischemic stroke.

Sorby-Adams A, Marian O, Bilecki I, Elms L, Yassi N, Hood R J Cereb Blood Flow Metab. 2024; 44(10):1759-1773.

PMID: 38546535 PMC: 11494854. DOI: 10.1177/0271678X241241907.

Substance P promotes the progression of bronchial asthma through activating the PI3K/AKT/NF-κB pathway mediated cellular inflammation and pyroptotic cell death in bronchial epithelial cells.

Li M, Zhong X, Xu W Cell Cycle. 2022; 21(20):2179-2191.

PMID: 35726575 PMC: 9519020. DOI: 10.1080/15384101.2022.2092166.

Elevated Substance P Is a Risk Factor for Postoperative Delirium in Patients with Hip Fracture.

Zhang W, Hu N, Zhang Y, Wang A Biomed Res Int. 2022; 2022:5320218.

PMID: 35402619 PMC: 8989553. DOI: 10.1155/2022/5320218.

Neurological heterotopic ossification: novel mechanisms, prognostic biomarkers and prophylactic therapies.

Wong K, Mychasiuk R, OBrien T, Shultz S, McDonald S, Brady R Bone Res. 2020; 8(1):42.

PMID: 33298867 PMC: 7725771. DOI: 10.1038/s41413-020-00119-9.

References

Folkers K, Horig J, Rosell S, Bjorkroth U . Chemical design of antagonists of substance P. Acta Physiol Scand. 1981; 111(4):505-6. DOI: 10.1111/j.1748-1716.1981.tb06771.x. View

Campos M, Calixto J . Neurokinin mediation of edema and inflammation. Neuropeptides. 2000; 34(5):314-22. DOI: 10.1054/npep.2000.0823. View

Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J . A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien). 2005; 148(3):255-68. DOI: 10.1007/s00701-005-0651-y. View

Sharma H, Nyberg F, Olsson Y, Dey P . Alteration of substance P after trauma to the spinal cord: an experimental study in the rat. Neuroscience. 1990; 38(1):205-12. DOI: 10.1016/0306-4522(90)90386-i. View

Kaplanski J, Asa I, Artru A, Azez A, Ivashkova Y, Rudich Z . LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats. Resuscitation. 2003; 56(2):207-13. DOI: 10.1016/s0300-9572(02)00371-4. View

Vink R, OConnor C, Nimmo A, Heath D . Magnesium attenuates persistent functional deficits following diffuse traumatic brain injury in rats. Neurosci Lett. 2002; 336(1):41-4. DOI: 10.1016/s0304-3940(02)01244-2. View

Bruno G, Tega F, Bruno A, Graf U, CORELLI F, Molfetta R . The role of substance P in cerebral ischemia. Int J Immunopathol Pharmacol. 2003; 16(1):67-72. DOI: 10.1177/039463200301600110. View

Ranga K, Krishnan R . Clinical experience with substance P receptor (NK1) antagonists in depression. J Clin Psychiatry. 2003; 63 Suppl 11:25-9. View

Kaplanski J, Pruneau D, Asa I, Artru A, Azez A, Ivashkova Y . LF 16-0687 Ms, a bradykinin B2 receptor antagonist, reduces brain edema and improves long-term neurological function recovery after closed head trauma in rats. J Neurotrauma. 2002; 19(8):953-64. DOI: 10.1089/089771502320317104. View

10.

Arvin B, Neville L, Barone F, Feuerstein G . The role of inflammation and cytokines in brain injury. Neurosci Biobehav Rev. 1996; 20(3):445-52. DOI: 10.1016/0149-7634(95)00026-7. View

11.

Vink R, Nimmo A . Multifunctional drugs for head injury. Neurotherapeutics. 2008; 6(1):28-42. PMC: 5084254. DOI: 10.1016/j.nurt.2008.10.036. View

12.

Annunziata P, Cioni C, Santonini R, Paccagnini E . Substance P antagonist blocks leakage and reduces activation of cytokine-stimulated rat brain endothelium. J Neuroimmunol. 2002; 131(1-2):41-9. DOI: 10.1016/s0165-5728(02)00262-x. View

13.

Souza D, Mendonca V, Castro M, Poole S, Teixeira M . Role of tachykinin NK receptors on the local and remote injuries following ischaemia and reperfusion of the superior mesenteric artery in the rat. Br J Pharmacol. 2002; 135(2):303-12. PMC: 1573137. DOI: 10.1038/sj.bjp.0704464. View

14.

Marmarou A, Nichols J, Burgess J, Newell D, Troha J, Burnham D . Effects of the bradykinin antagonist Bradycor (deltibant, CP-1027) in severe traumatic brain injury: results of a multi-center, randomized, placebo-controlled trial. American Brain Injury Consortium Study Group. J Neurotrauma. 1999; 16(6):431-44. DOI: 10.1089/neu.1999.16.431. View

15.

Szallasi A, Blumberg P . Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999; 51(2):159-212. View

16.

Nag S, Manias J, Stewart D . Pathology and new players in the pathogenesis of brain edema. Acta Neuropathol. 2009; 118(2):197-217. DOI: 10.1007/s00401-009-0541-0. View

17.

Ferrari M . Migraine. Lancet. 1998; 351(9108):1043-51. DOI: 10.1016/S0140-6736(97)11370-8. View

18.

Marmarou A, Fatouros P, Barzo P, Portella G, Yoshihara M, Tsuji O . Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients. J Neurosurg. 2000; 93(2):183-93. DOI: 10.3171/jns.2000.93.2.0183. View

19.

Bayliss W . On the origin from the spinal cord of the vaso-dilator fibres of the hind-limb, and on the nature of these fibres. J Physiol. 1901; 26(3-4):173-209. PMC: 1540518. DOI: 10.1113/jphysiol.1901.sp000831. View

20.

Chiang W, Chien C, Lin W, Lin S, Chen Y, Lai C . Early activation of bradykinin B2 receptor aggravates reactive oxygen species generation and renal damage in ischemia/reperfusion injury. Free Radic Biol Med. 2006; 41(8):1304-14. DOI: 10.1016/j.freeradbiomed.2006.07.011. View