title: Mediators of vascular and parenchymal mechanisms in secondary brain damage.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department Physiology, Ludwig-Maximilians University, Munich, Federal Republic of Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wahl
authors.forename: L
authors.initials: L
authors.lastname: Schilling
authors.forename: A
authors.initials: A
authors.lastname: Unterberg
authors.forename: A
authors.initials: A
authors.lastname: Baethmann
mesh_terms: D000209:Acute-Phase Proteins / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001920:Bradykinin / Q000502:physiology; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D001929:Brain Edema / Q000503:physiopathology*; D005609:Free Radicals; D016489:Head Injuries, Closed / Q000503:physiopathology*; D006632:Histamine / Q000502:physiology; D006801:Humans; D015289:Leukotrienes / Q000502:physiology
chemical_list: D000209:Acute-Phase Proteins; D005609:Free Radicals; D015289:Leukotrienes; D016718:Arachidonic Acid; D006632:Histamine; D001920:Bradykinin