ABSTRACT
Disruption of the blood-brain barrier (BBB) is found in many neurological diseases (Bradbury, 1979; Betz et al., 1994). Substances implicated in pathological damage to the BBB include the cytokines, tumor necrosis factor− α (TNF) and interleukin-1ß (IL-1), lipopolysaccharide (LPS), free radicals, and neutral proteases (Chan et al., 1984; Quagliarello et al., 1991; Andersson et al., 1992; Mayhan and Didion, 1996). Our laboratory has shown that matrix metalloproteinases (MMPs) are increased in brain injury, and are been implicated in the disruption of the BBB. Intracerebral injection of type IV collagenase causes attenuation of the capillary basal lamina and an increase in capillary permeability. The MMPs are induced in brain by the intracerebral injection of TNF. During a hemorrhagic and ischemic injury, gelatinase B (92-kDa type IV collagenase) and urokinase-type plasminogen activator are produced. Other substances, such as free radicals, are toxic to blood vessels. The combined effect of multiple toxic substances determines the injury to the capillary.
