Exp Mol Med.  2011 Feb;43(2):121-128. 10.3858/emm.2011.43.2.020.

Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats

• Won SM
• Lee JH
• Park UJ
• Gwag J
• Gwag BJ
• Lee YB

• KMID: 1097269
• DOI: http://doi.org/10.3858/emm.2011.43.2.020

Abstract

Blood cells are transported into the brain and are thought to participate in neurodegenerative processes following hypoxic ischemic injury. We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction proteins, occludin, and zonula occludens-1, and degeneration of endothelial cells in the CA1-2 areas. Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical production and endothelial cell degeneration. Our findings suggest that iron overload and iron-mediated free radical production cause loss of tight junction proteins and degeneration of endothelial cells, opening of the BBB after TFI.

Keyword

blood-brain barrier; deferoxamine; free radical; Neu2000; transient forebrain ischemia; iron

MeSH Terms

Animals
Blood-Brain Barrier/*metabolism
Capillary Permeability
Endothelial Cells/*metabolism
Evans Blue/metabolism
Free Radicals/metabolism
Hippocampus/*metabolism/pathology
Iron/*metabolism
Ischemic Attack, Transient/pathology/*physiopathology
Male
Membrane Proteins/metabolism
Rats
Rats, Sprague-Dawley