Mediators of brain edema and secondary brain damage.
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.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D001929:Brain Edema / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D007705:Kinins / Q000378:metabolism
D001095:Arachidonic Acids; D005971:Glutamates; D007705:Kinins; D016718:Arachidonic Acid; D018698:Glutamic Acid; D007610:Kallikreins