Brain Edema XIV pp 211-216

Substance P Immunoreactivity Increases Following Human Traumatic Brain Injury

  • Andrew C. Zacest
  • Robert Vink
  • Jim Manavis
  • Ghafar T. Sarvestani
  • Peter C. Blumbergs
Conference paper
Part of the Acta Neurochirurgica Supplementum book series (NEUROCHIRURGICA, volume 106)

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.

Keywords

Neurotrauma edema brain swelling neurogenic inflammation tachykinin substance P 

References

  1. 1.
    Black PH (2002) Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun 16:622–653PubMedCrossRefGoogle Scholar
  2. 2.
    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 12:565–572PubMedCrossRefGoogle Scholar
  3. 3.
    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 191:443–457PubMedCrossRefGoogle Scholar
  4. 4.
    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 356:327–344PubMedCrossRefGoogle Scholar
  5. 5.
    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 16:67–72PubMedGoogle Scholar
  6. 6.
    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 9:807–817PubMedCrossRefGoogle Scholar
  7. 7.
    Del Fiacco M, Dessi ML, Atzori MG, Levanti MC (1983) Substance P in the human brainstem. Preliminary results of its immunohistochemical localization. Brain Res 264:142–147PubMedCrossRefGoogle Scholar
  8. 8.
    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 48:187–203PubMedCrossRefGoogle Scholar
  9. 9.
    Donkin JJ, Turner RJ, Hassan I, Vink R (2007) Substance P in traumatic brain injury. Prog Brain Res 161:97–109PubMedCrossRefGoogle Scholar
  10. 10.
    Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451PubMedCrossRefGoogle Scholar
  11. 11.
    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) 97:297–305CrossRefGoogle Scholar
  12. 12.
    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 104:181–186PubMedCrossRefGoogle Scholar
  13. 13.
    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 94:4167–4170PubMedCrossRefGoogle Scholar
  14. 14.
    Kostyk SK, Kowall NW, Hauser SL (1989) Substance P immunoreactive astrocytes are present in multiple sclerosis plaques. Brain Res 504:284–288PubMedCrossRefGoogle Scholar
  15. 15.
    Lin RC (1995) Reactive astrocytes express substance-P immunoreactivity in the adult forebrain after injury. Neuroreport 7:310–312PubMedGoogle Scholar
  16. 16.
    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 96:5286–5291PubMedCrossRefGoogle Scholar
  17. 17.
    Maggi CA (1995) Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Prog Neurobiol 45:1–98PubMedCrossRefGoogle Scholar
  18. 18.
    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 86:5193–5197PubMedCrossRefGoogle Scholar
  19. 19.
    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 16:721–725PubMedCrossRefGoogle Scholar
  20. 20.
    Newbold P, Brain SD (1995) An investigation into the mechanism of capsaicin-induced oedema in rabbit skin. Br J Pharmacol 114:570–577PubMedCrossRefGoogle Scholar
  21. 21.
    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 38:40–47PubMedCrossRefGoogle Scholar
  22. 22.
    Ohlen A, Thureson-Klein A, Lindbom L, Persson MG, Hedqvist P (1989) Substance P activates leukocytes and platelets in rabbit microvessels. Blood Vessels 26:84–94PubMedGoogle Scholar
  23. 23.
    Reilly PL (2001) Brain injury: the pathophysiology of the first hours. ‘Talk and Die revisited’. J Clin Neurosci 8:398–403PubMedCrossRefGoogle Scholar
  24. 24.
    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 78:299–304PubMedCrossRefGoogle Scholar
  25. 25.
    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 21:798–811PubMedGoogle Scholar
  26. 26.
    Turner RJ, Blumbergs PC, Sims NR, Helps SC, Rodgers KM, Vink R (2006) Increased substance P immunoreactivity after reversible ischemic stroke. Acta Neurochir Suppl 96:263–266PubMedCrossRefGoogle Scholar
  27. 27.
    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 60:291–295PubMedCrossRefGoogle Scholar
  28. 28.
    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:PL7–11PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2010

Authors and Affiliations

  • Andrew C. Zacest
    • 3
  • Robert Vink
    • 1
    • 2
  • Jim Manavis
    • 2
  • Ghafar T. Sarvestani
    • 4
  • Peter C. Blumbergs
    • 1
    • 2
  1. 1.Discipline of Pathology, School of Medical SciencesUniversity of AdelaideAdelaideAustralia
  2. 2.Hanson Institute Centre for Neurological Diseases, Institute of Medical and Veterinary SciencesAdelaideAustralia
  3. 3.Disciplines of PathologyUniversity of AdelaideAdelaideAustralia
  4. 4.Division of HaematologyInstitute of Medical and Veterinary SciencesAdelaideAustralia

Personalised recommendations