Current concepts of brain edema. Review of laboratory investigations

Klatzo's classification of brain edema into two types, vasogenic and cytotoxic, has been in general use since 1967. The former involves overall brain swelling due to fluid entry from the vasculature because of openings in the blood-brain barrier (BBB), whereas the latter refers to cell swelling without any loss of the normal impermeability of the BBB. This review principally covers new work that identifies the intracellular swelling of astrocytes as a major form of cytotoxic edema seen in many different kinds of brain injury. The term edema should be retained because of its familiarity; however, because such intracellular swelling is usually not a response to toxins, it is suggested that the term cellular edema is preferable to cytotoxic edema. The difficulties involved in measuring cellular edema clinically are discussed, and the belief that a "pure" form of either edema is unlikely to exist. It is emphasized that the mechanisms and direct consequences of vasogenic and cellular edema are so different that the connection is mainly semantic. Studies conducted in vitro have identified several potentially damaging secondary consequences of astrocytic swelling. One of the most important of these seems likely to be the increased release of excitatory amino acids from swollen astrocytes. Potential mechanisms for inhibition of the increased release of amino acids have been identified in vitro and could prove therapeutically useful.