Unterberg A, Schmidt W, Wahl M, Baethmann A
Department of Neurosurgery, University of Munich, Federal Republic of Germany.
Adv Neurol. 1990;52:211-4.
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.
脑缺血后和脑肿瘤中白三烯会在脑组织中蓄积。因此，它们的释放可能导致在这些情况下观察到的血脑屏障损伤，进而引起脑水肿。研究了这些物质对软脑膜血管通透性的影响，以及抑制白三烯合成是否能减轻冷损伤性脑水肿。通过荧光显微镜研究了猫的软脑膜血管系统。通过颅骨窗向皮质灌注LTC4、LTD4或LTE4。静脉注射荧光素钠作为血脑屏障指示剂。高达2微摩尔的白三烯浓度并未导致血脑屏障指示剂向实质内渗漏。然而，所有测试的白三烯均使软脑膜动脉和静脉收缩。在冷损伤的兔子中研究了脑水肿的形成。BW755C是一种环氧化酶和脂氧化酶抑制剂，可阻止白三烯的形成，在创伤前后给予。对照动物仅接受生理盐水。BW755C在减轻冷损伤性水肿方面无效。对照动物的半球肿胀为7.8±1.1%，治疗动物为7.7±0.4%。即使以超过病理条件下水平的浓度将白三烯注入脑内，也不会引起屏障损伤，抑制白三烯合成也不会减轻血管源性水肿的形成。这些结果进一步证明白三烯不是该过程的介导化合物。
