Abstract
Under several pathological conditions such as trauma, incomplete ischemia, reperfusion after complete ischemia, tumor, and allergic or inflammatory diseases an opening of the blood-brain barrier (BBB) may occur. The extravasation inducing vasogenic oedema is obviously induced by the release of several autacoids as will be discussed in an updated review of items published previously.1–3 The mainly discussed mediators are histamine, bradykinin, arachidonic acid, free radicals, leukotrienes, and serotonin. Five criteria will be discussed for some favoured mediator candidates: 1) the effect on BBB permeability, 2) the vasomotor action which may affect driving force for transmural bulk flow, 3) the influence on oedema formation, 4) the actual concentration of the mediator in the tissue or in the interstitial space under pathological conditions and 5) the therapeutic results after treatment with specific inhibitors or antagonists.
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References
M. Wahl, A. Unterberg, Baethmann, and L. Schilling L, Mediators of blood-brain-barrier dysfunction and formation of vasogenic brain oedema, J. Cereb. Blood Flow Metab. 8:621 (1988).
M. Wahl, L. Schilling, A. Unterberg, and A. Baethmann, Mediators of vascular and parenchymal mechanisms in secondary brain damage, Acta Neurochir. 57, Suppl.:64 (1993).
M. Wahl, L. Schilling, A. Unterberg, and A. Baethmann, Opening of the blood-brain barrier by autacoids, in: “CNS Barriers and Modern CSF Diagnostics. Centennial of Quincke’s Lumbar Puncture”, K. Felgenhauer, M. Holzgraefe, and H.W. Prange, eds., VCH, Weinheim (1993).
L. Schilling and M. Wahl, Histaminergic effects on cerebral hemodynamics, in: “The Regulation of Cerebral Blood Flow”, J.W. Phillis, ed., CRC Press, Boca Raton (1993).
L. Schilling, A. Bultmann, and M. Wahl, Lack of effect of topically applied nicotine on pial arteriole diameter and blood brain barrier integrity in the cat, Clin. Invest. 70:210 (1992).
A. Findling, L. Schilling, A. Bultmann, and M. Wahl, Computerised image analysis in conjunction with fluorescence microscopy for the study of blood-brain barrier permeability in vivo, Pflügers Arch. 427:86 (1994).
L. Schilling and M. Wahl, Opening of the blood-brain barrier during cortical superfusion with histamine. Brain Res. 653:289 (1994).
A.M. Butt, H.C. Jones, and N.J. Abbott, Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study, J. Physiol. 429:47 (1990).
A.M. Butt and H.C. Jones, Effect of histamine and antagonists on electrical resistance across the blood-brain barrier in rat brain-surface microvessels, Brain Res. 569:100 (1992).
A.M. Butt, Electrical resistance measurements of blood-brain barrier permeability, This issue (1994).
A.S. Easton and P.A. Fraser, Regulation of cerebral microvascular brain permeability by histamine and CGRP, Proc. Int. Union Physiol. Sci. XXXII 88:17/P (1993).
F.R. Domer, S.B. Boertje, E.G. Bing, and I. Reddix, Histamine-and acetylcholine-induced changes in the permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats Neuropharmacology 22:615 (1983).
E. Dux, and F. Joó, Effects of histamine on brain capillaries. Fine structural and immunohistochemical studies after intracarotid infusion, Exp. Brain Res. 47:252 (1982).
P.M. Gross, G.M. Teasdale, D.I. Graham, W.J. Angerson, and A.M. Harper, Intra-arterial histamine increases blood-brain transport in rats, Am. J. Physiol. 243:H307 (1982).
A. Gulati, K.N. Dhawan, R. Shukla, R.C. Srimal, and B.N. Dawan, Evidence for the involvement of histamine in the regulation of blood-brain barrier permebility, Pharmacol. Res. Commun. 17:39 (1985).
R. Oishi, M. Baba, M. Nishibori, Y. Itoh, and K. Saeki, Involvement of central histaminergic and cholinergic systems in the morphine-induced increase in blood-brain barrier permeability to sodium fluorescein in mice, Naunyn-Schmiedeberg’s Arch. Pharmacol. 339:159 (1989).
P.M. Gross, A.M. Harper, and G.M. Teasdale, Cerebral circulation and histamine: 2. Responses of pial veins and arterioles to receptor agonists, J. Cereb. Blood Flow Metab. 1:219 (1981).
M. Wahl, and W. Kuschinsky, The dilating effect of histamine on pial arteries of cats and its mediation by H2 receptors, Circ. Res. 44:161 (1976).
R.G. Dacey, and J.E. Bassett, Histaminergic vasodilatation of intracerebral arterioles in the rat, J. Cereb. Blood Flow Metab. 7:327 (1987).
G. DeLey, J. Weyne, G. Demeester, and I. Leusen I, Response of local blood flow in the caudate nucleus of the cat to intraventricular administration of histamine, Stroke 13:499 (1982).
E.L. Orr, Cryogenic lesions induce a mast cell-dependent increase in cerebral histamine levels in the mouse, Neurochem. Pathol. 8:43 (1988).
S. Mohanty, P.K. Dey, H.S. Sharma, S. Singh, J.P.N. Chansouria, and Y. Olsson, Role of histamine in traumatic brain edema. An experimental study in the rat, J. Neurol. Sci. 90:87 (1989).
N. Adachi, R. Oishi, and K. Saeki, Changes in the metabolism of histamine and monoamines after occlusion of the middle cerebral artery in rats, J. Neurochem. 57:61 (1991).
N. Adachi, Y. Itoh, R. Oishi, and K. Saeki, Direct evidence for increased continuous histamine release in the striatum of conscious freely moving rats produced by middle cerebral artery occlusion, J. Cereb. Blood Flow Metab. 12:477 (1992).
L. Schilling and M. Wahl, Effects of antihistaminics on experimental brain edema, Acta Neurochir. Suppl. 60:79 (1994).
H.P.J.M. Leistra and W.D. Dietrich, Effect of histamine antagonist cimetidine on infarct size in the rat, J. Neurotrauma 10:83 (1993).
H.S. Sharma, F. Nyberg, J. Cervos-Navarro, and P.K. Dey, Histamine modulates heat stress-induced changes in blood-brain barrier permeability, cerebral blood flow, brain oedema and serotonin levels: an experimental study in conscious young rats, Neuroscience. 50:445 (1992).
F. Joó, J. Kovacs, P. Szerdahelyi, P. Temesvari, and A. Tosaki, Treatment with histamine receptor antagonists of ischemic brain edema, in: “Pharmacology of Cerebral Ischemia 1992”, J. Krieglstein and H. Oberpichler-Schwenk, eds., Wissenschaftliche Verlagsgesellschaft, Stuttgart (1992).
E. Csanda, Radiation brain edema, in: “Brain Edema,” J. Cervos-Navarro, and R. Ferszt, eds., Raven Press, New York (1980).
F. Joó, A. Zücs, and E. Csanda, Metiamide-treatment of brain oedema in animals exposed to 90yttrium irradiation, J. Pharm. Pharmacol. 28:162 (1976).
L. Sztriha, F. Joö, and P. Szerdahelyi, Histamine H2-receptors participate in the formation of brain edema induced by kainic acid in rat thalamus, Neurosci. Lett. 75:334 (1987).
A. Unterberg, M. Wahl, and A. Baethmann, Effects of bradykinin on permeability and diameter of pial vessels in vivo, J. Cereb. Blood Flow Metab. 4:574 (1984).
M. Wahl, A. Unterberg, and A. Baethmann, Intravital fluorescence microscopy for the study of blood-brain-barrier function, Int. J. Microcirc. Clin. Exp. 4:3 (1985).
M. Wahl and L. Schilling, Effects of bradykinin in the cerebral microcirculation, in: “The Regulation of Cerebral Blood Flow”, J.W. Phillis, ed., CRC Press, Boca Raton (1993).
P. Homayoun, and S.I. Harik, Bradykinin receptors of cerebral microvessels stimulate phosphoinositide turnover, J. Cereb. Blood Flow Metab. 11:557(1991).
M.A. Murray, D.D. Heistad, and W.G. Mayhan, Role of protein kinase C in bradykinin-induced increases in microvascular permeability, Circ. Res. 68:1340 (1991).
F.L. Guillot, and K.L. Audus, Angiotensin peptide regulation of fluid-phase endocytosis in brain microvessel endothelial cell monolayers, J. Cereb. Blood Flow Metab. 10:827 (1990).
N.J. Abbott and P.A. Revest, Control of brain endothelial permeability, Cerebrovasc. Brain Metab. Rev. 3:39 (1991).
S.-P. Olesen and C. Crone, Substances that rapidly augment ionic conductance of endothelium in cerebral venules, Acta Physiol. Scand. 127:233 (1986).
M. Wahl, A.R. Young, L. Edvinsson, and F. Wagner, Effects of bradykinin on pial arteries and arterioles in vitro and in situ, J. Cereb. Blood Flow Metab. 3:231 (1983).
E.T. Whalley, and M. Wahl, Analysis of bradykinin receptor mediating relaxation of cat cerebral arteries in vivo and in vitro, Naunyn-Schmiedeberg’s Arch. Pharmacol. 323:66 (1983).
T. Kamitani, M.H. Little, and E.F. Ellis, Effect of leukotrienes, 12-HETE, histamine, bradykinin, and 5-hydroxytryptamine on in vivo rabbit cerebral arteriolar diameter, J. Cereb. Blood Flow Metab. 5:554 (1985).
H.A. Kontos, E.P. Wei, J.T. Povlishock, and C.W. Christman, Oxygen radicals mediate the cerebral arteriolar dilatation from arachidonate and bradykinin in cats, Circ. Res. 55:295 (1984).
H.A. Kontos, E.P. Wei, R.C. Kukreja, E.F. Ellis, and M.L. Hess, Differences in endothelium-dependent cerebral dilation by bradykinin and acetylcholine, Am. J. Physiol. 258:H1261 (1990).
R.G. Dacey, J.E. Bassett, and M. Takayasu, Vasomotor responses of rat intracerebral arterioles to vasoactive intestinal peptide, substance P, neuropeptide Y, and bradykinin, J. Cereb. Blood Flow Metab. 8:254 (1988).
A. Unterberg, A. Baethmann, The kallikrein-kinin system as mediator on vasogenic brain edema. Part 1: Cerebral exposure to bradykinin and plasma, J. Neurosurg. 61:87 (1984).
I.R. Whittle, I.R. Piper, and J.D. Miller, The role of bradykinin in the etiology of vasogenic brain edema and perilesional brain dysfunction, Acta Neurochir. 115:53 (1992).
M. Wahl, A. Unterberg, E.T. Whalley, A. Baethmann, A.R. Young, L. Edvinsson, and F.F.W. Wagner, Cerebrovascular effects of bradykinin, in: “Neural Regulation of Brain Circulation”, C. Owman, J.E. Hardebo, eds., Elsevier, New York (1986).
M. Wahl, A. Unterberg, E.T. Whalley, A. Baethmann, A.R. Young, L. Edvinsson, and F. Wagner, Effect of bradykinin on cerebral hemodynamics and blood-brain-barrier function in: “Peptidergic Mechanisms in the Cerebral Circulation”, L. Edvinsson, and J. McCulloch, eds., Horwood, Chichester (1987).
K. Maier-Hauff, A.J. Baethmann, M. Lange, L. Schürer, and A. Unterberg, The kallikrein-kinin system as mediator in vasogenic brain edema. Part 2: Studies on kinin formation in focal and perifocal brain tissue, J. Neurosurg. 61:97 (1984).
E.F. Ellis, J. Chao, and M.L. Heizer, Brain kininogen following experimental brain injury: evidence for a secondary event, J. Neurosurg. 71:437 (1989).
J. Xu, C.Y. Hsu, H. Junker, S. Chao, E.L. Hogan, and J. Chao, Kininogen and kinin in experimental spinal cord injury, 7. Neurochem. 57:975 (1991).
T. Kamiya, Y. Katayama, F. Kashiwagi, and A. Terashi, The role of bradykinin in mediating ischémic brain edema in rats, Stroke 24:571 (1993).
A. Unterberg, C. Dautermann, A. Baethmann, and W. Müller-Esterl, The kallikrein-kinin system as mediator in vasogenic brain edema, Part 3: Inhibition of the kallikrein-kinin system in traumatic brain swelling, J. Neurosurg. 64:269 (1986).
E.F. Ellis, S.A. Holt, E.P. Wei, and H.A. Kontos HA, Kinins induce abnormal vascular reactivity, Am. J. Physiol. 255:H397 (1988).
A. Unterberg, M. Wahl, F. Hammersen, and A. Baethmann, Permeability and vasomotor response of cerebral vessels during exposure to arachidonic acid, Acta Neuropathol. 73:209 (1987).
P.H. Chan, R. A. Fishman, J. Caronna, J.W. Schmidley, G. Priolieau, and J. Lee, Induction of brain edema following intracerebral injection of arachidonic acid, Ann. Neurol. 13:625 (1983).
S. Wakai, K. Aritake, T. Asano, and K. Takakura K, Selective destruction of the outer leaflet of the capillary endothelial membrane after intracerebral injection of arachidonic acid in the rat, Acta Neuropathol. 58:303 (1982).
E.P. Wei, M.D. Ellison, H.A. Kontos, and J.T. Povlishock, O2 radicals in arachidonate-induced increased blood-brain barrier permeability to proteins. Am. J. Physiol. 251:H693 (1986).
L. Sztriha and A.L. Betz, Oleic acid reversibly opens the blood brain barrier, Brain Res 550:25 (1991).
H.A. Kontos, E.P. Wei, J.T. Povlishock, W.D. Dietrich, C.J. Magiera, and E.P. Ellis, Cerebral arteriolar damage by arachidonic acid and prostaglandin G2, Science 209:1242 (1980).
K.L. Black, and J.T. Hoff, Leukotrienes increase blood-brain barrier permeability following intraparenchymal injections in rats, Ann. Neurol. 18:349 (1985).
W. Lo and P. Clair, Leukopenia reduces blood-brain barrier (BBB) damage in acute cerebral inflammation, Soc. Neurosci. Abst. 19:225 (1993).
D.W. Busija, and D.D. Heistad, Effects of indomethacin on cerebral blood flow during hypercapnia in cats, Am. J. Physiol. 244:H519 (1983).
A. Unterberg, A. Baethmann, M. Wahl, L. Schürer, and A. Marmarou, New aspects in the formation of vasogenic brain edema, in: “Surgical Research. Recent Concepts and Results”, A. Baethmann, and U. Messmer, eds., Springer, Heidelberg (1987).
A. Unterberg, T. Polk, E. Ellis, and A. Marmarou, Enhancement of infusion induced brain edema by mediator compounds, in: “Brain Edema. Pathogenesis, Imaging and Therapy”, Adv Neurol 52, D.M. Long, ed., Raven Press, New York (1990).
A. Baethmann, K. Maier-Hauff, L. Schürer, M. Lange, C. Guggenbichler, W. Vogt, K. Jacob, and O. Kempski, Release of glutamate and of free fatty acids in vasogenic brain edema, J. Neurosurg. 70:578 (1989).
N.G. Bazan, and E.B. Rodriguez de Turco, Membrane lipids in the pathogenesis of brain oedema. Phospholipids and arachidonic acid, the earliest membrane components changed at the onset of ischemia, in: “Brain Edema” J. Cervos-Navarro, R. Ferszt, eds., Raven Press, New York, (1980).
K.K. Bhakoo, H.A. Crockard, and P.T. Lascelles, Regional studies of changes in brain fatty acids following experimental ischaemia and reperfusion in the gerbil. J. Neurochem. 43:1025 (1984).
E.P. Wei, C.W. Christman, H.A. Kontos, and J.T. Povlishock, Effects of oxygen radicals on cerebral arterioles, Am. J. Physiol 248:H157 (1985).
S.P. Olesen, Free oxygen radicals decrease electrical resistance of microvascular endothelium in brain, Acta Physiol. Scand. 129:181 (1987).
P.H. Chan, J.W. Schmidley, R.A. Fishman, and S.M. Longar, Brain injury, edema, and vascular permeability changes induced by oxygen-derived free radicals, Neurology 34:315 (1984).
A. Unterberg, M. Wahl, and A. Baethmann, Effects of free radicals on permeability and vasomotor response of cerebral vessels, Acta Neuropathol. 76:238 (1988).
W.I. Rosenblum, Effects of free radical generation on mouse pial arterioles: probable role of hydroxylradicals, Am. J. Physiol. 245:H139 (1983).
H.B. Demopoulos, E.S. Flamm, M.L. Seligman, J.A. Mitamura, and J. Ransohoff, Membrane perturbations in central nervous system injury: theoretical basis for free radical damage and a review of the experimental data, in: “Neural Trauma”, A.J. Popp, R.S. Bourke, L.R. Nelson, and H.K. Kimelberg, eds., Raven Press, New York (1979).
H.A. Kontos and E.P. Wei, Superoxide production in experimental brain injury, J. Neurosurg. 64:803 (1986).
B.K. Siesjö, G. Bendek, T. Koide, E. Westerberg, and T. Wieloch, Influence of acidosis on lipid peroxidation in brain tissues in vitro, J. Cereb. Blood Flow Metab. 5:253 (1985).
O. Suzuki, and K. Yagi, Formation of lipoperoxide in brain edema induced by cold injury, Experientia 30:248 (1974).
J. Lundgren, H. Zhang, C.D. Agardh, M.L. Smith, P.J. Evans, B. Halliwell, and B.K. Siesjö, Acidosis-induced ischémic brain damage: Are free radicals involved? J. Cereb. Blood Flow Metab. 11:587(1991).
P.H. Chan, S. Longar, and R.A. Fishman, Protective effects of liposome-entrapped Superoxide dismutase on posttraumatic brain edema, Ann. Neurol. 21:540 (1987).
D.M. Long, “Brain Edema. Pathogenesis, Imaging and Therapy”, Adv Neurol 52, Raven Press, New York (1990).
Y. Ando, M. Inoue, M. Hirota, Y. Morino, and S. Araki, Effect of Superoxide dismutase derivative on cold-induced brain edema, Brain Res. 477:286 (1989).
W.M. Armstead, R. Mirro, O.P. Thelin, M. Shibata, S.L. Zuckerman, D.R. Shanklin, D.W. Busija, and C.W. Leffler, Polyethylene glycol Superoxide dismutase and catalase attenuate increases in blood-brain barrier permeability after ischemia in piglets, Stroke 23:755 (1992).
P.H. Chan, G.Y. Yang, S.F. Chen, E. Carlson, and C.J. Epstein, Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase, Ann. Neurol. 29:482 (1991).
T.D. Oury, C.A. Piantadosi, and J.D. Crapo, Cold-induced brain edema in mice, J. Biol. Chem. 268:15394(1993).
J.S. Beckmann, J. Chen, H. Ischiropoulos, and K. A. Conger, Inhibition of nitric oxide synthesis and cerebral protection, in: “Pharmacology of Cerebral Ischemia 1992”, J. Krieglstein and H. Oberpichler-Schwenk, eds., Wissenschaftliche Verlagsgesellschaft, Stuttgart (1992).
D.A. Pelligrino, Saying NO to cerebral ischemia, J. Neurosurg. Anesth. 5:221 (1993).
A. Unterberg, W. Schmidt, M. Wahl, E.F. Ellis, A. Marmarou, and A. Baethmann, Evidence against leukotrienes as mediators of brain edema, J. Neurosurg. 74:773 (1991).
A. Unterberg, W. Schmidt, T. Polk, M. Wahl, E. Ellis, A. Marmarou, and A. Baethmann, Evidence against leukotrienes as mediators of brain edema, J. Cereb. Blood Flow Metab. 7, Suppl. 1:S625 (1987).
A. Unterberg, W. Schmidt, M. Wahl, and A. Baethmann, “Role of Leukotrienes as Mediator Compounds in Brain Edema”, in: “Brain Edema. Pathogenesis, Imaging and Therapy”, Adv Neurol 52, D.M. Lond, ed., Raven Press, New York (1990).
X.-Y. Hua, S.-E. Dahlen, J.M. Lundberg, S. Hammarström, and P. Hedqvist, Leukotrienes C4, D4 and E4 cause widespread and extensive plasma extravasation in the guinea pig, Naunyn-Schmiedeberg’s Arch. Pharmacol. 330:136(1985).
T. Baba, K.L. Black, K. Ikezaki, K. Chen, and D.P. Becker, Intracarotid infusion of leukotriene C4 selectively increases blood-brain barrier permeability after focal ischemia in rats, J. Cereb. Blood Flow Metab. 11:638(1991).
C.C. Chio, T. Baba, and K.L. Black, Selective blood-tumor barrier disruption by leukotrienes, J. Neurosurg. 77:407 (1992).
T. Baba, C.C. Chio, and K.L. Black, The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors, J. Neurosurg. 77:403 (1992).
W.I. Rosenblum, Constricting effect of leukotrienes on cerebral arterioles of mice, Stroke 16:262 (1985).
D.W. Busija, C.W. Leffler, and D.G. Beasley, Effects of leukotrienes C4, D4 and E4 on cerebral arteries of newborn pigs, Pediatr. Res. 20:973 (1986).
A. Dembinska-Kiec, T. Simmet, and B. A. Peskar, Formation of leukotriene C4-like material by rat brain tissue, Eur. J. Pharmacol. 99:57 (1984).
M.A. Moskowitz, K.J. Kiwak, K. Hekimian, and L. Levine, Synthesis of compounds with properties of leukotrienes C4 and D4 in gerbil brains after ischemia and reperfusion, Science 224:886 (1984).
K.J. Kiwak, M.A. Moskowitz, and L. Levins, Leukotriene production in gerbil brain after ischemic insult, subarachnoid hemorrhage, and concussive injury, J. Neurosurg. 62:865 (1985).
K.L. Black, J.T. Hoff, J.E. McGillicuddy, and S.S. Gebarski, Increased leukotriene C4 and vasogenic edema surrounding brain tumors in humans, Ann. Neurol. 19:592 (1986).
R.J. Dempsey, M.W. Roy, K. Meyer, D.E. Cowen, and M.E. Maley, Development of cyclooxygenase and lipoxygenase metabolites of arachidonic acid after transient cerebral ischemia, J. Neurosurg. 64:118(1986).
S.T. Chen, C.Y. Hsu, E.L. Hogan, P.V. Halushka, O.I. Linet, and F.M. Yatsu, Thromboxane, prostacyclin, and leukotrienes in cerebral ischemia, Neurology 36:466 (1988).
P. Megyeri, C.S. Abraham, P. Temesvari, J. Kovacs, T. Vas, and C.P. Speer, Recombinant human tumor necrosis factor α constricts pial arterioles and increases blood brain barrier permeability in newborn piglets, Neurosci. Lett. 148:137 (1992).
K.S. Kim, C.A. Wass, A.S. Cross, and S.M. Opal, Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat, Lymphokine Cytokine Res. 11:293(1992).
G.A. Rosenberg, P.G. McGuire, J.E. Dencoff, E.Y. Estrada, A.N. Clark, and W.G. Stetler-Stevenson, Metalloproteinases and serine proteinases link cytokines to blood-brain barrier injury in rat, Soc. Neurosci. Abst. 19:692 (1993).
Y. Yamasaki, T. Suzuki, H. Yamaya, N. Matsuura, H. Onodera, and K. Kogure, Possible involvement of interleukin-1 in ischémic brain edema formation, Neurosci. Lett. 142:45 (1992).
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Wahl, M., Schilling, L., Unterberg, A., Baethmann, A. (1995). Autacoids as Mediators of Vasogenic Brain Oedema. In: Greenwood, J., Begley, D.J., Segal, M.B. (eds) New Concepts of a Blood—Brain Barrier. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1054-7_15
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