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 resistant cells, using a rat ischemic brain model. Frozen sections of the brain 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 were also studied. P-gp positive endothelial cells disappeared in the ischemic lesion by post-ischemic Day 3. Factor VIII-positive regenerating capillaries were first observed on Day 3 without P-gp expression when the brain edema reached a maximum. P-gp positive endothelial cells began 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 cells showed a similar pattern as that of gamma-GTP, and its induction is associated with GFAP-positive reactive astrocytes. These results suggest that P-gp might play an important role in maintaining the BBB function in conjunction with glial cells.
Department of Neurosurgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
K
K
Samoto
K
K
Ikezaki
N
N
Yokoyama
M
M
Fukui
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001812:Blood-Brain Barrier / Q000235:genetics* / Q000502:physiology; D001921:Brain / Q000098:blood supply; D001929:Brain Edema / Q000235:genetics* / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1