Role of leukotrienes as mediator compounds in brain edema.
Leukotrienes accumulate in brain tissue after cerebral ischemia and in brain tumors. Thus, their release might contribute to the blood-brain barrier damage observed under these conditions and, hence, brain edema. The effect of these substances on the permeability of pial vessels and whether inhibition of LT synthesis reduces cold injury brain edema were studied. The pial vasculature of cats was studied by fluorescence microscopy. The cortex was superfused with LTC4, LTD4, or LTE4 via a cranial window. Na(+)-fluorescein was intravenously administered as blood-brain barrier indicator. LT concentrations up to 2 microM did not induce any leakage of the blood-brain barrier indicator into the parenchyma. However, all LTs tested constricted pial arteries and veins. Brain edema formation was studied in rabbits with cold injury. BW755C, an inhibitor of cyclooxygenase and lipoxygenase preventing formation of LTs, was given before and after trauma. Control animals received saline only. BW755C was ineffective in attenuating cold injury edema. Hemispheric swelling in control animals was 7.8 +/- 1.1%, and 7.7 +/- 0.4% in animals with treatment. LTs, even when administered to the brain in concentrations exceeding levels occurring under pathological conditions, did not induce barrier damage, nor did inhibition of LT synthesis attenuate formation of vasogenic edema. The results provide further evidence against LTs as mediator compounds of this process.
Unterberg
A
A
Department of Neurosurgery, University of Munich, Federal Republic of Germany.
Schmidt
W
W
Wahl
M
M
Baethmann
A
A
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D001930:Brain Injuries / Q000150:complications; D002415:Cats; D003080:Cold Temperature / Q000009:adverse effects; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D015289:Leukotrienes / Q000096:biosynthesis* / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009929:Organ Size; D010841:Pia Mater / Q000098:blood supply; D011817:Rabbits
D005456:Fluorescent Dyes; D015289:Leukotrienes; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine