CHANGES OF ACTIVITY AND ULTRASTRUCTURAL-LOCALIZATION OF ALKALINE-PHOSPHATASE IN CEREBRAL CORTICAL MICROVESSELS OF RAT AFTER SINGLE INTRAPERITONEAL ADMINISTRATION OF MERCURIC-CHLORIDE

Inorganic mercury salts administered systemically at low mg/ml doses p roduce neurotoxic effects without penetrating the cerebral microvascul ar endothelial cells which form the blood-brain barrier (BBB). This ph enomenon promoted investigations testing a hypothesis relating inorgan ic mercury-induced brain dysfunction to its interference with the BBB transport. In the present study, we tested the effect of a single i.p. administration of mercuric chloride (MC) (6 mg/kg body weight) on the activity and ultrastructural localization of cerebral alkaline phosph atase (AP), a cerebromicrovascular marker enzyme primarily located on luminal plasmalemma of endothelial cells. At 1h after MC administratio n, light microscopy revealed a virtual absence of AP in cerebral corti cal layers II and III, and its dramatic reduction in the remaining lay ers. Electron microscopy confirmed the disappearance of the AP reactio n product from luminal endothelial cell membranes, and luminal phasmal emma revealed pinocytic vesicles and invaginations likely to manifest changes in BBB transport At 18h posttreatment, a moderate enzyme activ ity appeared on abluminal endothelial plasmalemma and on basement memb rane, but remained absent from luminal plasmalemma. A similar picture persisted through day 5 post-treatment. The inhibition and subsequent translocation of AP activity from luminal to abluminal site and the ac companying ultrastructural changes are typical of the formation of ''l eaky'' microvessels, previously reported for a variety of neuropatholo gical conditions associated with BBB damage. (C) 1994 Intox Press, Inc .