EXPRESSION OF TISSUE-PLASMINOGEN ACTIVATOR IN CEREBRAL CAPILLARIES - POSSIBLE FIBRINOLYTIC FUNCTION OF THE BLOOD-BRAIN-BARRIER

PREVIOUS WORK HAS shown that tissue plasminogen activator (tPA) is a k ey enzyme in the control of fibrinolysis within the vascular system. T he sources of brain tPA and the mechanisms by which tPA secretion and production occur within cerebral microcirculation are not well establi shed. In this study, expression of tPA was investigated in cerebral ca pillaries and capillary-depleted brain isolated from cortices of 4- to 5-week-old rats and guinea pigs. In both species, a single tPA band o f M(T) 67,000 was detected in cerebral capillaries by Western blot ana lysis. The tPA signal was absent from capillary-depleted brain. These results were corroborated at the messenger ribonucleic acid level. Rev erse transcription-polymerase chain reaction analysis revealed the pre sence of tPA complementary deoxyribonucleic acid in samples derived fr om cerebral microvessels and demonstrated very low or undetectable tPA expression in capillary-depleted brain. Immunohistochemical analysis confirmed tPA localization in endothelial cells of brain capillaries. We conclude that microvascular endothelium, i.e., the blood-brain barr ier, may have a role in promoting plasmin-dependent fibrinolysis in br ain microcirculation, Delineation of the molecular mechanisms of blood -brain barrier-mediated fibrinolysis will likely contribute to future stroke prevention efforts.