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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)

Abstract

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.

Keywords

Vasogenic brain edema mediator compounds bloodbrain barrier vasomotor response 

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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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