Mediators of Vascular and Parenchymal Mechanisms in Secondary Brain Damage

  • M. Wahl
  • L. Schilling
  • A. Unterberg
  • A. Baethmann
Conference paper
Part of the Acta Neurochirurgica book series (NEUROCHIRURGICA, volume 57)


Several putative mediators of vasogenic brain edema will be considered with respect to the following criteria: 1) their effect on blood-brain barrier (BBB) permeability, 2) their vasomotor actions which may increase driving forces for transmural bulk flow, 3) their influence on edema formation, 4) their actual tissue concentration in pathological states, and 5) the therapeutic results after specific treatment.

Bradykinin (BK) can induce brain edema by increasing BBB permeability to small solutes and enhancing blood pressure in the microcirculation due to arterial dilatation and venous constriction. Its interstitial concentration is enhanced after experimental trauma. Since kallikrein inhibitors reduce brain swelling all criteria favour BK as a mediator of vasogenic edema.

Arachidonic acid (AA) opens BBB also for large tracers but exerts only small vasomotor effects. The edema formation is associated with an increase of the AA concentration in the interstitial space. However, convincing therapeutic results on inhibition of AA are still lacking. In addition to the formation of vasogenic edema AA has been found to induce cytotoxic edema. From experiments dealing with the vasomotor effects Ellis et al. (Am J Physiol 255: H397–H400,1988) concluded an interaction of BK and AA in brain injury. However, our own results do not favour this hypothesis since we found divergent vasomotor and permeability effects of BK and AA.

Histamine (HA) opens BBB unspecifically and dilates cerebral vessels, mechanisms by which edema formation can be explained. Further requirements, such as formation of histamine in injured brain tissue as well as therapeutical inhibition of edema from mechanical iniury by a histamine antagonist, are met supporting a mediator function of the agent in vasogenic brain edema.

Leukotrienes (LT) are potent constrictors of cerebral arteries and their tissue concentrations are increased in pathological states. However, they do not induce extravasation or edema formation. Correspondingly, lipoxygenase inhibitors are not effetive in experimental brain injury.

Free radicals (FR) are released under several pathological conditions but induce only irregular tracer leakage. Formation of edema may be facilitated by some arterial dilatation. Further therapeutic studies are necessary. Moreover, FR have been found to induce cytotoxic edema by similar mechanisms as reported for AA.

Serotonin may increase BBB permeability under certain conditions. However, it appears not to be involved in edema generation since negative results have been described for the other criteria.

Taken together, the requirements of identification of a mediator compound of brain edema are met in the case of bradykinin, arachidonic acid, histamine, and, probably in case of the free radicals. Evidence is less convincing for leukotrienes or serotonin. It should be noted in this context that the above mediator compounds are likely to enhance formation of brain edema not only by their specific pathophysiological properties but also on the basis of mutual activation of a mediator network.


Vasogenic brain edema mediator compounds bloodbrain barrier vasomotor response 


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  1. 1.
    Baethmann A, Oettinger W, Rothenfußer W, Kempski O, Unterberg A, Geiger R (1980) Brain edema factors:current state with particular reference to plasma constituents andglutamate. In: Cervos-Navarro J, Ferszt R (eds) Brain edema. Adv neurol 28. Raven, NewYork, pp 171–195Google Scholar
  2. 2.
    Baethmann A, Maier-Hauff K, Schürer L, Lange M, Guggenbichler C, Vogt W, Jacob K, Kempski O (1989) Release of glutamate and of free fatty acids in vasognic brain edema. J Neurosurg 70:578–591PubMedCrossRefGoogle Scholar
  3. 3.
    Bazan NG, Rodriguez de Turco EB (1980) Membrane lipids in the pathogenesis of brain edema. Phospholipids and arachidonic acid, the earliest membrane components changed at the onset ofischemia. In: Cervos-Navarro J, Ferszt R (eds) Brain edema. Adv neurol 28. Raven, New York, pp 197–205Google Scholar
  4. 4.
    Bhakoo KK,Crockard HA, Lascelles FT (1984) Regional studies of changes in brain fattyacids following experimental ischaemia and reperfusion in the gerbil. JNeurochem 43: 1025–1031CrossRefGoogle Scholar
  5. 5.
    BlackKL (1984) Leukotriene C4 induces vasogenic cerebral edema in rats. ProstaglandLeukotr Med 14: 339–340CrossRefGoogle Scholar
  6. 6.
    BlackKL,Hoff JT(1985) Leukotrienes increase blood-brain barrier permeability followingintraparenchymal injections in rats. Ann Neurol 18: 349–351PubMedCrossRefGoogle Scholar
  7. 7.
    Black KL, Hoff JT, McGillicuddy JE (1986) Increasedleukotriene C4 and vasogenic edema surrounding brain tumors in humans.Ann Neurol 19: 592–595PubMedCrossRefGoogle Scholar
  8. 8.
    Busija DW,Heistad DD (1983) Effects of indomethacin on cerebral blood flow duringhypercapnia in cats. Am J Physiol 244:H5I9–H524Google Scholar
  9. 9.
    Busija DW,Leffler CW, Beasley G (1986) Effects of leukotrienes C4, D4and E4 on cerebral arteries on newborn pigs. Pediat Res 20: 973– 976PubMedCrossRefGoogle Scholar
  10. 10.
    Chan PH, Fishman RA (1984)The role of arachidonic acid in vasogenic brain edema. Federation Proc 43:210–213Google Scholar
  11. 11.
    Chan PH, FishmanRA, Caronna J, Schmidley JW, Priolieau G, Lee J (1983) Induction of brain edemafollowing intracerebral injection of arachidonic acid. Ann Neurol 13: 625–632PubMedCrossRefGoogle Scholar
  12. 12.
    Chan PH,Schmidley JW, Fishman RA, Longar SM (1984) Brain injury, edema, and vascularpermeability changes induced by oxygen-derived free radicals. Neurology 34:315–320PubMedGoogle Scholar
  13. 13.
    Chan PH, LongarS, Fishman RA (1987) Protective effects of liposome-entrapped Superoxidedismutaseon posttraumatic brain edema. Ann Neurol 21: 540–547PubMedCrossRefGoogle Scholar
  14. 14.
    Csanda E (1980)Radiation brain edema. In: Cervos-Navarro J, Ferszt R (eds) Brain edema. Advneurol 28. Raven, New York, pp 125–146Google Scholar
  15. 15.
    Dacey RG, BassettJE(1987)Histaminergic vasodilatation of intra-cerebral arterioles in the rat. J CerebBlood Flow Metabol 7: 327–331CrossRefGoogle Scholar
  16. 16.
    Dacey RG, BassettJE,TakayasuM (1988) Vasomotor responses of rat intracerebral arterioles to vasoactiveintestinal peptide, substance p, neuropeptide Y, and bradykinin. J Cereb BloodFlow Metabol 8: 254–261CrossRefGoogle Scholar
  17. 17.
    DeLey G, Weyne J,Demeester G, Leusen I (1982) Response of local blood flow in the caudatenucleus of the cat to intraventricular administration of histamine. Stroke 13:499–504CrossRefGoogle Scholar
  18. 18.
    Demopoulos HB, Flamm ES,SeligmanML, Mitamura JA,RansohoffJ (1979) Membrane perturbations in central nervous system injury: theoreticalbasis for free radical damage and a review of the experimental data. In: Popp AJ, Bourke RS,Nelson LR, Kimelberg HK (eds) Neural trauma. Raven, New York, pp 63–78Google Scholar
  19. 19.
    Domer FR, Boertje SB,Bing EG, Reddix I (1983) Histamine and acetylcholine-induced changes in thepermeability of the blood-brain barrier of normotensive and spontaneouslyhypertensive rats. Neuropharmacology 22: 615–619PubMedCrossRefGoogle Scholar
  20. 20.
    Dux E, Joó F(1982) Effects of histamine on brain capillaries. Fine structural andimmunohistochemical studies after intracarotid infusion. Exp Brain Res 47:252–258PubMedCrossRefGoogle Scholar
  21. 21.
    Edvinsson L,Hardebo JE,MacKenzieET,StewartM (1977) Dual action of serotonin on pial arterioles in situ and theeffect of propranolol. Blood Vessels 14: 366–371PubMedGoogle Scholar
  22. 22.
    Edvinsson L,Gross PM, Mohamed A (1983) Characterization of histamine receptors in catcerebral arteries in vitro and in situ. J Pharmacol Exp Ther 225:168–175PubMedGoogle Scholar
  23. 23.
    Ellis EF, Heizer ML, Chao J (1987)The kallikrein-kinin system in normal an injured brain. J Cereb Blood FlowMetabol 7 [Suppll]: S 631Google Scholar
  24. 24.
    Ellis EF, HoltSA, Wei EP,Kontos HA(1988) Kinins induce abnormal vascular reactivity. Am J Physiol 255: H397–H400PubMedGoogle Scholar
  25. 25.
    Fenske A, Sinterhauf K, Reulen HJ(1976) The role of monoamines in the development of cold-induced edema. In:Pappius HM,FeindlW (eds) Dynamics of brain edema. Springer, Berlin Heidelberg New York, pp150–154CrossRefGoogle Scholar
  26. 26.
    Gabbiani G,Basonnel MC,MajnoG (1970) Intra-arterial injections of histamine, serotonin, or bradykinin: atopographic study of vascular leakage. Proc Soc Exp Biol Med 135: 447–452PubMedGoogle Scholar
  27. 27.
    Gardiner M,Nilsson B, Rehncrona S, Siesjö BK (1981) Free fatty acids in the rat brain inmoderate and severe hypoxia. J Neurochem 36: 1500–1505PubMedCrossRefGoogle Scholar
  28. 28.
    Grome JJ, HarperAM (1983) The effects of serotonin on local cerebral blood flow. J Cereb BloodFlow Metabol 3: 71–77CrossRefGoogle Scholar
  29. 29.
    Grome JJ, HarperAM (1985) Serotonin depression of local cerebral glucose utilization aftermonoamine oxidase inhibition. J Cereb Blood Flow Metabol 5: 473–475CrossRefGoogle Scholar
  30. 30.
    Grome JJ, HarperAM (1986) Local cerebral glucose utilization following indoleamine- and piperazinecontaining 5-hydroxytryptamine agonists. J Neurochem 46: 117–124PubMedCrossRefGoogle Scholar
  31. 31.
    Gross PM, HarperAM, Teasdale GM (1981) Cerebral circulation and histamine: 2. responses of pialveins and arterioles to receptor agonists. J Cereb Blood Flow Metabol 1:219–225CrossRefGoogle Scholar
  32. 32.
    Gross PM,Teasdale GM, Graham DI, Angerson WJ, Harper AM (1982) Intra-arterialhistamine increases blood-brain transport in rats. Am J Physiol 243: H307–H317PubMedGoogle Scholar
  33. 33.
    Hardebo JE, Owman Ch, WiklundL (1981) Influence of neurotransmitter monoamines and neurotoxic analogues onmorphologic blood-brain barrier function. In: Cervos-Navarro J, Fritschka E(eds) Cerebral microcirculation and metabolism. Raven, New York, pp 177–180Google Scholar
  34. 34.
    Harper AM,MacKenzie ET(1977a)Cerebral circulatory and metabolic effects of 5-hydroxytryptamine inanaesthetized baboons. J Physiol (London) 271: 721–733Google Scholar
  35. 35.
    Harper AM,MacKenzie ET(1977b)Effects of 5-hydroxytryptamine on pial arteriolar calibre in anaesthetizedcats. J Physiol (London) 271: 735–746Google Scholar
  36. 36.
    Hua XY, DahlenSE, Lundberg JM, Hammarström S, Hedquist P (1985) Leukotrienes C4, D4and E4 cause widespread and extensive plasma extravasation in theguinea pig. Naunyn Schmiedebergs Arch Pharmacol 330: 136–141PubMedCrossRefGoogle Scholar
  37. 37.
    Joó F, Zücs A,Csanda E (1976) Metiamide-treatment of brain edema in animals exposed to 90yttriumirradiation. J Pharm Pharmacol 28: 162– 163PubMedCrossRefGoogle Scholar
  38. 38.
    Kamitani T,Little MH, Ellis EF (1985a) Evidence for a possible role of the brainkallikrein-kinin system in the modulation of the cerebral circulation. Circ Res57: 545–552PubMedGoogle Scholar
  39. 39.
    Kamitani T,Little MH, Ellis EF (1985b) Effect of leukotrienes, 12-HETE, histamine,bradykinin, and 5-hydroxytryptamine on in vivo rabbit cerebralarteriolar diameter. J Cereb Blood Flow Metabol 5: 554–559CrossRefGoogle Scholar
  40. 40.
    Kiwak KJ,Moskowitz MA, Levine L (1985) Leukotriene production in gerbil brain afterischemic insult, subarachnoid hemorrhage, and concussive injury. J Neurosurg62: 865–869PubMedCrossRefGoogle Scholar
  41. 41.
    Kontos HA (1985) Oxygenradicals in cerebral vascular injury. Circ Res 57: 508–516PubMedGoogle Scholar
  42. 42.
    Kontos HA, Wei EP (1986)Superoxideproductionin experimental brain injury. J Neurosurg 64: 803–807PubMedCrossRefGoogle Scholar
  43. 43.
    Kontos HA, Wei EP,Povlishock JT, Dietrich WD, Magiera CJ, Ellis EP (1980) Cerebral arteriolardamage by arachidonic acid and prostaglandin G2. Science 209: 1242–1245PubMedCrossRefGoogle Scholar
  44. 44.
    Kontos HA, Wei EP,Povlishock JT, Christman CW (1984) Oxygen radicals mediate the cerebralarteriolar dilatation from arachidonate and bradykinin in cats. Circ Res 55:295–303PubMedGoogle Scholar
  45. 45.
    Long DM (ed)(1990) Brain edema, pathogenesis, imaging, and therapy. Adv neurol 52. Raven,New YorkGoogle Scholar
  46. 46.
    Maier-Hauff K,Baethmann AJ, LangeM, Schürer L, Unterberg A(1984) The kallikrein-kinin system as mediator in vasogenic brain edema. Part2: studies on kinin formation in focal and perifocal brain tissue. J Neurosurg61: 97–106PubMedCrossRefGoogle Scholar
  47. 47.
    Martins AN, DoyleTF, WrightSJ,BassBG(1980)Response of cerebral circulation to topical histamine. Stroke 11: 469–476PubMedCrossRefGoogle Scholar
  48. 48.
    Mohanty S, DeyPK, Sharma HS,SinghS, Chansouria JPN, Olsson Y (1989) Role of histamine in traumatic brain edema.An experimental study in the rat. J Neurolog Sci 90: 87–97CrossRefGoogle Scholar
  49. 49.
    Moskowitz MA,Kiwak KJ, Hekimian K, Levine L (1984) Synthesis of compounds with properties ofleukotrienes C4 and D4 in gerbil brains after ischemia andreperfusion. Science 224: 886–889PubMedCrossRefGoogle Scholar
  50. 50.
    Olesen SP (1985)A calcium-dependent reversible increase in micro-vessels in frog brain inducedby serotonin. J Physiol (London) 361: 103–113Google Scholar
  51. 51.
    Olesen SP (1987)Free oxygen radicals decrease electrical resistance of microvascularendothelium in brain. Acta Physiol Scand 129: 181–188PubMedCrossRefGoogle Scholar
  52. 52.
    Olesen SP, CroneC (1986) Substances that rapidly augment ionic conductance of endothelium incerebral venules. Acta Physiol Scand 127: 233–241PubMedCrossRefGoogle Scholar
  53. 53.
    Orr EL (1988)Cryogenic lesions induce a mast cell-dependent increase in cerebral histaminelevels in the mouse. Neurochem Pathol 8: 43–51Google Scholar
  54. 54.
    Pappius H (1986)Mechanisms underlying functional disturbances in traumatized brain. In:Mchedelishvilli GJ, Cervos Navarro J, Hossmann KA, Klatzo I(eds) Brain edema. A pathogenic analysis. Akademiai Kiado, Budapest, pp 282–286Google Scholar
  55. 55.
    Pappius HM, WolfeLS (1983a) Involvement of serotonin and catecholamines in functional depressionof traumatized brain. J Cereb Blood Flow Metabol 3 [Suppl 1]: S226–S227CrossRefGoogle Scholar
  56. 56.
    Pappius HM, WolfeLS (1983b) Functional disturbances in brain following injury: Search forunderlying mechanisms. Neurochem Res 8: 63–72PubMedCrossRefGoogle Scholar
  57. 57.
    Pappius HM, Dadoun R (1987)Effects of injury on the in doleamines in cerebral cortex. J Neurochem 49:321–325PubMedCrossRefGoogle Scholar
  58. 58.
    RosenblumWI(1983) Effects of free radicals generation on mouse pial arterioles: probablerole of hydroxyl radicals. Am J Physiol 245: Hl39–H142Google Scholar
  59. 59.
    RosenblumWI(1985) Constricting effect of leukotrienes on cerebral arterioles of mice.Stroke 16: 262–263PubMedCrossRefGoogle Scholar
  60. 60.
    Saria A, LundbergJM, Skofitsch G, Lembeck F (1983) Vascular protein leakage in various tissuesinduced by substance P, capsaicin, bradykinin, serotonin, histamine and byantigen challenge. Naunyn-Schmiedebergs Arch Pharmacol 324: 212– 218PubMedCrossRefGoogle Scholar
  61. 61.
    Schilling L,Ksoll E, WahlM(1987a) Effects of histamine on vasomotor response and permeability ofextraparenchymal cerebral vessels. J Cereb Blood Flow Metabol 7 [Suppl]: S 506Google Scholar
  62. 62.
    Schilling L,Ksoll E, WahlM(1987b) Increase of pial vessel diameter and permeability during corticalsuperfusion with histamine. Pflügers Arch 408 [Suppl 1]: R20Google Scholar
  63. 63.
    Schilling L,Ksoll E, WahlM(1987c) Vasomotor and permeability effects of histamine in cerebral vessels.Int J Microcirc Clin Exp 6: 70Google Scholar
  64. 64.
    Sharma HS, Dey PK (1986)Probable involvement of 5 hydroxytryptamine in increased permeability ofblood-brain barrier under heat stress in young rats. Neuropharmacology 25:161–167PubMedCrossRefGoogle Scholar
  65. 65.
    Siesjö BK (1981)Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metabol1: 155–185CrossRefGoogle Scholar
  66. 66.
    Siesjö BK, BendekG, Koide T, WesterbergE, Wieloch T (1985)Influence of acidosis on lipid peroxidation in brain tissues in vitro. JCereb Blood Flow Metabol 5: 253–258CrossRefGoogle Scholar
  67. 67.
    Solomon LS (1974)Failure of buffered 5-hydroxytryptamine to increase brain capillarypermeability to albumin in monkeys. JNeurosurg 40: 717–725CrossRefGoogle Scholar
  68. 68.
    Suzuki O, Yagi K(1974) Formation of lipoperoxide in brain edema induced by cold injury.Experientia 30: 248PubMedCrossRefGoogle Scholar
  69. 69.
    UnterbergA,Baethmann A (1984) The kallikrein-kinin system as mediator on vasogenic brainedema. Part 1: cerebral exposure to bradykinin and plasma. J Neurosurg 61:87–96PubMedCrossRefGoogle Scholar
  70. 70.
    UnterbergA, Wahl M, Baethmann A(1983) Effects of bradykinin on cerebrovascular permeability and resistance. JCereb Blood Flow Metabol 3 [Suppl 1]: S234–S235Google Scholar
  71. 71.
    UnterbergA, Wahl M, Baethmann A(1984) Effects of bradykinin on permeability and diameter of pial vessels invivo. J Cereb Blood Flow Metabol 4: 574–585CrossRefGoogle Scholar
  72. 72.
    Unterberg A, Wahl M, Baethmann A(1985) Arachidonic acid induces opening of the blood-brain barrier. Int JMicrocirc Clin Exp 4: 302Google Scholar
  73. 73.
    UnterbergA,Dautermann C, Baethmann A, Müller-Esterl W (1986) Thekallikrein-kinin system as mediator in vasogenic brain edema. J Neurosurg 64:269–276PubMedCrossRefGoogle Scholar
  74. 74.
    UnterbergA, Wahl M, Hammersen F,Baethmann A (1987a) Permeability and vasomotor response of cerebral vesselsduring exposure to arachidonic acid. Acta Neuropathol 73: 209–219PubMedCrossRefGoogle Scholar
  75. 75.
    UnterbergA,Baethmann A, WahlM, Schürer L, Marmarou A(1987b) New aspects in the formation of vasogenic brain edema. In: Baethmann A,Messmer K (eds) Surgical research. Recent concepts and results. Springer,Berlin Heidelberg New York Tokyo, pp 3–8CrossRefGoogle Scholar
  76. 76.
    UnterbergA,Schmidt W, Polk T, Wahl M, Ellis E, Marmarou A, Baethmann A (1987c) Evidenceagainst leukotrienes as mediators of brain edema. J Cereb Blood Flow Metabol 7[Suppl 1]:S625CrossRefGoogle Scholar
  77. 77.
    UnterbergA, Wahl M, Baethmann A(1988) Effects of free radicals on permeability and vasomotor response ofcerebral vessels. Acta Neuropathol 76: 238–244PubMedCrossRefGoogle Scholar
  78. 78.
    UnterbergA,Polk T, Ellis E, Marmarou A (1989a) Enhancement of infusion induced brain edemaby mediator compounds. In: Long DM (ed) Adv Neurol 52 (1990). Raven, New York,pp 355–358Google Scholar
  79. 79.
    UnterbergA,Schmidt W, WahlM,Baethmann A (1989b) Role of leukotrienes as mediator compounds in brain edema:In: Long DM (ed) Adv neurol 52 (1990). Raven, New York, pp 211–214Google Scholar
  80. 80.
    Wahl M (1982) Theeffect of opiate-like substances and bradykinin on cerebrovascular resistancein cats. In: Heistad DD, Marcus ML (eds) Cerebral blood flow. Effects of nervesand neurotransmitters. Elsevier, New York, pp 235–241Google Scholar
  81. 81.
    Wahl M, Kuschinsky W(1976) The dilating effect of histamine on pial arteries of cats and itsmediation by H2-receptors. Circ Res 44: 161–165Google Scholar
  82. 82.
    Wahl M, UnterbergA,Baethmann A (1983a) The effect of bradykinin on the cerebrovascular resistanceand blood brain barrier permeability. In: Hossmann KA, Klatzo I(eds) Cerebrovascular transport mechanisms. Acta Neuropathol [Suppl] 8: 132–133Google Scholar
  83. 83.
    Wahl M, Young AR, Edvinsson L,Wagner F (1983b) Effects of bradykinin on pial arteries and arterioles invitro and in situ. J Cereb Blood Flow Metabol 3: 231–237CrossRefGoogle Scholar
  84. 84.
    Wahl M, UnterbergA,Baethmann A (1985a) Intravital fluorescence microscopy for the study ofblood-brain-barrier function. Int J Microcirc Clin Exp 4: 3–18PubMedGoogle Scholar
  85. 85.
    Wahl M, UnterbergA,Baethmann A (1985b) Effects of arachidonic acid on blood-brain barrierfunction. In: Dietz H, Brock M, Klinger M (eds) Extra-intercranialvascular anastomoses. Microsurgery at the edge of the tentorium. Adv neurosurg13. Springer, Berlin Heidelberg New York Tokyo, pp 323–325CrossRefGoogle Scholar
  86. 86.
    Wahl M, UnterbergA,Whalley ET,BaethmannA, Young AR,EdvinssonL, Wagner FFW (1986a) Cerebrovascular effects of bradykinin. In: Owman C,Hardebo JE(eds)Neural regulation of brain circulation. Elsevier, New York, pp 419–430Google Scholar
  87. 87.
    Wahl M, Unterberg A, Baethmann A (1986b) The effects of free radicals and leukotrienes on blood-brain-barrier function. Int J Microcirc ClinExp 5: 93Google Scholar
  88. 88.
    Wahl M, Unterberg A, Whalley ET, Baethmann A, Young AR, Edvinsson L, Wagner F (1987) Effect of bradykinin on cerebralhemodynamics and blood-brain-barrier function. In: Edvinsson L, McCulloch J (eds) Peptidergic mechanisms in the cerebral circulation. Horwood, Chichester, pp 166–190Google Scholar
  89. 89.
    Wahl M, Unterberg A, Baethmann A, Schilling L (1988) Mediators ofblood-brain-barrier dysfunction and formation of vasogenic brain edema. J Cereb Blood Flow Metabol 8: 621–634CrossRefGoogle Scholar
  90. 90.
    Wakai S, Aritake K, Asano T, Takakura K (1982) Selective destruction of the outer leaflet of the capillary endothelial membraneafter intracerebral injection of arachidonic acid in the rat. ActaNeuropathol 58: 303–306Google Scholar
  91. 91.
    Wei EP, Ellis EF, Kontos HA (1980) Role of prostaglandins in pial arteriolarresponse to CO2 and hypoxia. Am J Physiol 238: H226–H23OPubMedGoogle Scholar
  92. 92.
    Wei EP, Christman CW, Kontos HA, Povlishock JT (1985) Effects of oxygen radicals on cerebralarterioles. Am J Physiol 248:H157–H162PubMedGoogle Scholar
  93. 93.
    Wei EP, Ellison MD, Kontos HA, Povlishock JT (1986) O2 radicals inarachidonate-induced increased blood-brain barrier permeability to proteins. Am J Physiol 251: H693–H699PubMedGoogle Scholar
  94. 94.
    Westergaard E (1975) The effect of serotonin,norepinephrine and cyclic AMP on the blood-brain barrier. J Ultrastruct Res50: 383Google Scholar
  95. 95.
    Westergaard E (1977) The blood-brain barrier tohorseradish peroxidase under normal and experimental conditions. Acta Neuropathol 39:181–188PubMedCrossRefGoogle Scholar
  96. 96.
    Whalley ET, Wahl M (1983) Analysis of bradykinin receptor mediatingrelaxation of cat cerebral arteries in vivo and in vitro. Naunyn-Schmiedebergs Arch Pharmacol 323: 66–71PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • M. Wahl
    • 1
  • L. Schilling
    • 1
  • A. Unterberg
    • 2
  • A. Baethmann
    • 3
  1. 1.Department PhysiologyLudwig-Maximilians UniversityMunichFederal Republic of Germany
  2. 2.Department NeurosurgeryLudwig-Maximilians UniversityMunichFederal Republic of Germany
  3. 3.Institute for Surgical ResearchLudwig-Maximilians UniversityMunichFederal Republic of Germany

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