P-glycoprotein expression in brain capillary endothelial cells after focal ischemia in rat

Acta Neurochir Suppl (Wien). 1994;60:257-60. doi: 10.1007/978-3-7091-9334-1_68.

Abstract

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Animals
  • Astrocytes / pathology
  • Blood-Brain Barrier / genetics*
  • Blood-Brain Barrier / physiology
  • Brain / blood supply
  • Brain Edema / genetics*
  • Brain Edema / pathology
  • Brain Ischemia / genetics*
  • Brain Ischemia / pathology
  • Capillaries / pathology
  • Endothelium, Vascular / pathology*
  • Gene Expression Regulation / physiology
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1