Baethmann A, Maier-Hauff K, Kempski O, Unterberg A, Wahl M, Schürer L
Department of Neurosurgery, Klinikum Grosshadern, Munich, West Germany.
Crit Care Med. 1988 Oct;16(10):972-8. doi: 10.1097/00003246-198810000-00008.
Progress is our understanding of the roles of vasogenic and cytotoxic brain edema in secondary brain damage can be expected from studies of the ability of biochemical factors to open the blood-brain barrier, derange the microcirculation, and cause cell swelling and necrosis. Mediator compounds are considered to form or to become released in an area of primarily damaged brain (necrosis) and to enter the cerebral parenchyma through the broken blood-brain barrier from the intravascular space. Many biochemical factors must be considered. We suggested three criteria for determining the roles of mediators: a) they must inflict brain tissue damage, b) they must occur in pathologic concentrations or in compartments not normally present, and c) specific inhibition should attenuate secondary brain damage. These requirements are met by the kallikrein-kinin system and by glutamate. In the case of arachidonic acid and its many metabolites, the concept is difficult to test because fatty acids may be active only if not bound to proteins, and therapeutic inhibition might be difficult. A variety of mediators may enhance each other in a cascade manner by various initiating reactions that might be amenable for pharmacologic inhibition.
随着我们对血管源性脑水肿和细胞毒性脑水肿在继发性脑损伤中作用的理解不断深入，有望从生物化学因素打开血脑屏障、扰乱微循环以及导致细胞肿胀和坏死能力的研究中获得进展。介导化合物被认为在原发性脑损伤（坏死）区域形成或释放，并通过破损的血脑屏障从血管内空间进入脑实质。必须考虑许多生物化学因素。我们提出了确定介导物作用的三个标准：a）它们必须造成脑组织损伤，b）它们必须以病理浓度出现或存在于正常不存在的隔室中，c）特异性抑制应减轻继发性脑损伤。激肽释放酶-激肽系统和谷氨酸满足这些要求。就花生四烯酸及其许多代谢产物而言，这一概念难以检验，因为脂肪酸可能只有在未与蛋白质结合时才具有活性，而且治疗性抑制可能很困难。多种介导物可能通过各种可能适合药物抑制的起始反应以级联方式相互增强。
