Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-11T04:27:29.716Z Has data issue: false hasContentIssue false
  • English
  • Français

The immune system mediates blood-brain barrier damage; possible implications for pathophysiology of neuropsychiatric illnesses

Published online by Cambridge University Press:  18 September 2015

Y.D. Van Der Werf ,
M.J.L. De Jongste  and
G.J. Ter Horst
Get access Rights & Permissions [Opens in a new window]

Summary

In this investigation the effects of immune activation on the brain are characterized. In order to study this, we used a model for chronic immune activation, the myocardial infarction, and intravenous injections with the pro-inflammatory cytokine Tumour Necrosis Factor alpha (TNF-α). The incentive for this study is the observation that myocardial infarction is accompanied by behavioural and neuronal abnormalities. The effects of myocardial infarction on the brain and its functioning are widespread. In order to examine the mechanism through which this interaction occurs, a group of rats underwent an experimentally induced myocardial infarction whereafter immunohistochemistry was performed on slices of the brain. This experiment revealed regional serum protein extravasation, pointing to leakage of the blood-brain barrier. This process occurred in certain cortical, subcortical and hindbrain areas in discrete patches. The leakage was co-localized with the expression of the immune activation marker ICAM-1. A second group of rats was therefore injected with TNF-α, a major pro-inflammatory cytokine, to assess the involvement of the immune system in the effects shown. This procedure rendered the same results. It is concluded that myocardial infarction may interfere with the integrity of the blood-brain barrier and possibly with brain functioning through activation of the immune system. The relevance for pathophysiological processes is discussed.

Keywords

Cytokinesimmune activationheartbrainintercellular adhesion moleculeCytokinesimmuunactivatiemyocardinfarcthersenenhartintercellulair adhesie-molecule
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 7 , Issue 4 , December 1995 , pp. 114 - 121
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 1995

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Literatuur

1.Packer, M. Neurohumoral interactions and adaptations in congestive heart failure. Circulation 1988; 77: 721–30.CrossRefGoogle Scholar
2.Hirsch, AT, Dzau, VJ, Creager, MA. Baroreceptor function in congestive heart failure: effect on neurohumoral activation of vascular resistance. Circulation 1987; 75 suppl IV: 36–48.Google ScholarPubMed
3.Patel, KP, Zhang, PL, Krukoff, TL. Alterations in brain hexokinase activity associated with heart failure in rats. Am J Physiol 1993; 265: R923-8.Google ScholarPubMed
4.Cassem, NH. Psychological aspects of myocardial infarction. Med Clin N-Am 1977; 61: 711–21.CrossRefGoogle ScholarPubMed
5.Schleifer, SJ, Macari-Hinson, MM, Coyle, DA, Slater, WR, Kahn, M, Gorlin, R, Zucker, HD. The nature and course of depression following myocardial infarction. Arch Intern Med 1989; 149: 1785–9.CrossRefGoogle ScholarPubMed
6.Ladwig, KH, Röll, G, Breithardt, G, Budde, T, Borggrefe, M. Postinfarction depression and incomplete recovery 6 months after acute myocardial infarction. The Lancet 1994; 343: 20–3.CrossRefGoogle ScholarPubMed
7.Roose, SP, Dalack, GW. Treating the depressed patient with cardiovascular problems. J Clin Psychiatry 1992; 53(9, suppl): 25–31.Google ScholarPubMed
8.Schaie, KW. Intellectual development and adulthood. In: Birren, JE, Schaie, KW, eds. Handbook of the Psychology of Aging. San Diego: Acad Press, 1990: 291–304.CrossRefGoogle Scholar
9.Lipsey, JR, Forrester, AW, Robinson, RG. Depression following stroke and myocardial infarction. In: Weintraub, MI, Fass, AE, eds. Heart and Brain: Interaction of cardiac and neurologic disease. California: PMA 1991: 191–204.Google Scholar
10.Sole, MJ, Hussain, MN, Lixfeld, W. Activation of brain catechol-aminergic neurons by cardiac vagal afférents during acute myocardial ischemia in the rat. Circ Res 1980; 47: 166–72.CrossRefGoogle ScholarPubMed
11.Entman, ML, Michael, L, Rossen, RDet al.Inflammation in the course of early myocardial ischemia. FASEB J 1991; 5: 2529–37.CrossRefGoogle ScholarPubMed
12.Mazzone, A, De Servi, S, Rivecuti, Get al.Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. Circulation 1993; 88: 358–63.CrossRefGoogle ScholarPubMed
13.Vaddi, K, Nicolini, FA, Mehta, P, Mehta, JL. Increased secretion of Tumour Necrosis Factor-a and Interferon-y by mononuclear leukocytes in patients with ischemic heart disease. Relevance in superoxide anion generation. Circulation 1994; 90: 694–9.CrossRefGoogle Scholar
14.Fan, J, Shimokama, T, Haraoka, S, Tokunaga, O, Watanabe, T. Monocyte-endothelial cell interactions in vitro with reference to the influence of interleukin-1 and tumor necrosis factor. Biol Cell 1993;79: 17–26.CrossRefGoogle Scholar
15.Sluiter, W, Pietersma, A, Lamers, JMJ, Koster, JF. Leukocyte adhesion molecules on the vascular endothelium: their role in the pathogenesis of cardiovascular disease and the mechanisms underlying their expression. J cardiovasc Pharmacol 1993; 22/4: S37-44.CrossRefGoogle ScholarPubMed
16.Hansen, PR, Svendsen, JH, Hoyer, S, Kharazmi, A, Bendtzen, K, Haunso, S. Tumor necrosis factor-a increases myocardial microvascular transport in vivo. Am J Physiol 1944; 266: H60-7.Google Scholar
17.Ter Horst, GJ, Van den Brink, A, Homminga, SA, Hautvast, RWM, Rakhorst, G, Mettenleiter, TC, De Jongste, MJL, Lie, KI, Korf, J. Transneuronal viral labeling of the heart left ventricle controlling pathways. Neuroreport 1993; 4/12: 1307-10.CrossRefGoogle ScholarPubMed
18.Luiten, PGM, Ter Horst, GJ, Steffens, AB. The hypothalamus, intrinsic connections and outflow pathways to the endocrine system in relation to the control of feeding and metabolism. Progr Neurobiol 1987; 28: 1–54CrossRefGoogle Scholar
19. Ter Horst, GJ, Hautvast, RWM, Van den Brink, A, Homminga, SA, De Jongste, MJL, Lie, KI, Korf, J. Labelling of differential neuronal populations in the medulla oblongata and the thoracic spinal cord after inoculation of the various parts of the rat heart with pseudo-rabies virus. J Comp Neurol (submitted), 1995Google Scholar
20.Eikelenboom, P, Zhan, S-S, Van Gool, WA, Allsop, D. Inflammatory mechanisms in Alzheimer's disease. Trends pharmacol Sci 1994; 15: 447-50CrossRefGoogle ScholarPubMed
21.Dickson, DW, Sunhee, CL, Mattiace, LA, Yen, S-HC, Brosnan, C. Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia 1993; 7:84–92CrossRefGoogle ScholarPubMed