P-GLYCOPROTEIN EXPRESSION IN BRAIN CAPILLARY ENDOTHELIAL-CELLS AFTER FOCAL ISCHEMIA IN RAT

We investigated the time kinetics of P-glycoprotein (P-gp), a membrane bound drug efflux pump for many anti-cancer drugs in multidrug resist ant cells, using a rat ischemic brain model. Frozen sections of the br ain were studied immunohistochemically with anti-Factor VIII antibody for endothelial cells, with anti-glial fibrillary acidic protein (GFAP ) antibody for reactive astrocytes, and with MC6-4 monoclonal antibody for P-gp. A putative blood-brain barrier (BBB) marker, gamma-glutamyl transpeptidase (gamma-GTP), and the progression of the brain edema we re also studied. P-gp positive endothelial cells disappeared in the is chemic lesion by post-ischemic Day 3. Factor VIII-positive regeneratin g capillaries were first observed on Day 3 without P-gp expression whe n the brain edema reached a maximum. P-gp positive endothelial cells b egan to reappear on Day 5, and were detected in all endothelial cells by Day 8. The time kinetics of P-gp expression in the endothelial cell s showed a similar pattern as that of gamma-GTP, and its induction is associated with GFAP-positive reactive astrocytes. These results sugge st that P-gp might play an important role in maintaining the BBB funct ion in conjunction with glial cells.