Abstract
Recent experimental evidence suggests that neuropeptides, and in particular substance P (SP), are released following traumatic brain injury (TBI) and may play a significant role in the aetiology of cerebral edema and increased intracranial pressure. Whether SP may play a similar role in clinical TBI remains unknown and was investigated in the current study. Archival post-mortem material was selected from patients who had sustained TBI, had died and had undergone post-mortem and detailed neuropathological examination (n = 13). A second cohort of patients who had died, but who showed no neuropathological abnormality (n = 10), served as case controls. Changes in SP immunoreactivity were examined in the cerebral cortex directly beneath the subdural haematoma in 7 TBI cases and in proximity to contusions in the other 6 cases. Increased SP perivascular immunoreactivity was observed after TBI in 10/13 cases, cortical neurones in 12/13 and astrocytes in 10/13 cases. Perivascular axonal injury was observed by amyloid precursor protein (APP) immunoreactivity in 6/13 TBI cases. Co-localization of SP and APP in a small subset of perivascular fibres suggests perivascular axonal injury could be a mechanism of release of this neuropeptide. The abundance of SP fibres around the human cerebral microvasculature, particularly post capillary venules, together with the changes observed following TBI in perivascular axons, cortical neurones and astrocytes suggest a potentially important role for substance P in neurogenic inflammation following human TBI.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Black PH (2002) Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun 16:622–653
Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ (1995) Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 12:565–572
Brimijoin S, Lundberg JM, Brodin E, Hokfelt T, Nilsson G (1980) Axonal transport of substance P in the vagus and sciatic nerves of the guinea pig. Brain Res 191:443–457
Brown JL, Liu H, Maggio JE, Vigna SR, Mantyh PW, Basbaum AI (1995) Morphological characterization of substance P receptor-immunoreactive neurons in the rat spinal cord and trigeminal nucleus caudalis. J Comp Neurol 356:327–344
Bruno G, Tega F, Bruno A, Graf U, Corelli F, Molfetta R, Barucco M (2003) The role of substance P in cerebral ischemia. Int J Immunopathol Pharmacol 16:67–72
Castro-Obregon S, Del Rio G, Chen SF, Swanson RA, Frankowski H, Rao RV, Stoka V, Vesce S, Nicholls DG, Bredesen DE (2002) A ligand–receptor pair that triggers a non-apoptotic form of programmed cell death. Cell Death Differ 9:807–817
Del Fiacco M, Dessi ML, Atzori MG, Levanti MC (1983) Substance P in the human brainstem. Preliminary results of its immunohistochemical localization. Brain Res 264:142–147
Dimitriadou V, Buzzi MG, Theoharides TC, Moskowitz MA (1992) Ultrastructural evidence for neurogenically mediated changes in blood vessels of the rat dura mater and tongue following antidromic trigeminal stimulation. Neuroscience 48:187–203
Donkin JJ, Turner RJ, Hassan I, Vink R (2007) Substance P in traumatic brain injury. Prog Brain Res 161:97–109
Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451
Ghabriel MN, Lu MX, Leigh C, Cheung WC, Allt G (1999) Substance P-induced enhanced permeability of dura mater microvessels is accompanied by pronounced ultrastructural changes, but is not dependent on the density of endothelial cell anionic sites. Acta Neuropathol (Berl) 97:297–305
Hokfelt T, Meyerson B, Nilsson G, Pernow B, Sachs C (1976) Immunohistochemical evidence for substance P-containing nerve endings in the human cortex. Brain Res 104:181–186
Kennedy PG, Rodgers J, Jennings FW, Murray M, Leeman SE, Burke JM (1997) A substance P antagonist, RP-67, 580, ameliorates a mouse meningoencephalitic response to Trypanosoma brucei brucei. Proc Natl Acad Sci USA 94:4167–4170
Kostyk SK, Kowall NW, Hauser SL (1989) Substance P immunoreactive astrocytes are present in multiple sclerosis plaques. Brain Res 504:284–288
Lin RC (1995) Reactive astrocytes express substance-P immunoreactivity in the adult forebrain after injury. Neuroreport 7:310–312
Liu H, Mazarati AM, Katsumori H, Sankar R, Wasterlain CG (1999) Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. Proc Natl Acad Sci USA 96:5286–5291
Maggi CA (1995) Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Prog Neurobiol 45:1–98
Mantyh PW, Johnson DJ, Boehmer CG, Catton MD, Vinters HV, Maggio JE, Too HP, Vigna SR (1989) Substance P receptor binding sites are expressed by glia in vivo after neuronal injury. Proc Natl Acad Sci USA 86:5193–5197
Nakagawa N, Sano H, Iwamoto I (1995) Substance P induces the expression of intercellular adhesion molecule-1 on vascular endothelial cells and enhances neutrophil transendothelial migration. Peptides 16:721–725
Newbold P, Brain SD (1995) An investigation into the mechanism of capsaicin-induced oedema in rabbit skin. Br J Pharmacol 114:570–577
Nimmo AJ, Cernak I, Heath DL, Hu X, Bennett CJ, Vink R (2004) Neurogenic inflammation is associated with development of edema and functional deficits following traumatic brain injury in rats. Neuropeptides 38:40–47
Ohlen A, Thureson-Klein A, Lindbom L, Persson MG, Hedqvist P (1989) Substance P activates leukocytes and platelets in rabbit microvessels. Blood Vessels 26:84–94
Reilly PL (2001) Brain injury: the pathophysiology of the first hours. ‘Talk and Die revisited’. J Clin Neurosci 8:398–403
Stjernholm Y, Sennstrom M, Granstom L, Ekman G, Johansson O (1999) Protein gene product 9.5 – immunoreactive nerve fibers and cells in human cervix of late pregnant, postpartal and non-pregnant women. Acta Obstet Gynecol Scand 78:299–304
Stumm R, Culmsee C, Schafer MK, Krieglstein J, Weihe E (2001) Adaptive plasticity in tachykinin and tachykinin receptor expression after focal cerebral ischemia is differentially linked to gabaergic and glutamatergic cerebrocortical circuits and cerebrovenular endothelium. J Neurosci 21:798–811
Turner RJ, Blumbergs PC, Sims NR, Helps SC, Rodgers KM, Vink R (2006) Increased substance P immunoreactivity after reversible ischemic stroke. Acta Neurochir Suppl 96:263–266
Zachrisson O, Lindefors N, Brene S (1998) A tachykinin NK1 receptor antagonist, CP-122, 721–1, attenuates kainic acid-induced seizure activity. Brain Res Mol Brain Res 60:291–295
Ziche M, Morbidelli L, Geppetti P, Maggi CA, Dolara P (1991) Substance P induces migration of capillary endothelial cells: a novel NK-1 selective receptor mediated activity. Life Sci 48:PL7–11
Acknowledgment
Supported, in part, by the Motor Accident Comm-ission of SA.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag/Wien
About this paper
Cite this paper
Zacest, A.C., Vink, R., Manavis, J., Sarvestani, G.T., Blumbergs, P.C. (2010). Substance P Immunoreactivity Increases Following Human Traumatic Brain Injury. In: Czernicki, Z., Baethmann, A., Ito, U., Katayama, Y., Kuroiwa, T., Mendelow, D. (eds) Brain Edema XIV. Acta Neurochirurgica Supplementum, vol 106. Springer, Vienna. https://doi.org/10.1007/978-3-211-98811-4_39
Download citation
DOI: https://doi.org/10.1007/978-3-211-98811-4_39
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-98758-2
Online ISBN: 978-3-211-98811-4
eBook Packages: MedicineMedicine (R0)