Intercellular adhesion molecule-1 and blood-spinal cord barrier disruption in central nervous system radiation injury.
Central nervous system (CNS) injury is a major dose-limiting toxicity that limits the effectiveness of radiation therapy. Blood-brain barrier (BBB) disruption and white matter necrosis are prominent features. Increased expression of intercellular adhesion molecule-1 (ICAM-1) accompanies and is believed to be important in BBB disruption in other CNS injuries. Our aim was to assess the expression of ICAM-1 and its relationship to regions of blood-spinal cord barrier (BSCB) disruption in the irradiated rat spinal cord. ICAM-1 protein was detected by immunohistochemistry and quantified by digital image analysis. Cells expressing ICAM-1 were identified. BSCB disruption was assessed by immunohistochemical detection of serum albumin. ICAM-1 expression localized predominantly to vascular endothelium and increased in white matter but not in grey matter at 24 hours and 17 to 20 weeks after 22 Gy. A dose response was observed from 16 to 20 Gy. ICAM-1 expression colocalized with regions of BSCB disruption. ICAM-1 expression was also observed in glia, a majority of which were astrocytes. The parallel dose response, time course, and spatial distribution of ICAM-1 expression and albumin leakage suggest a role for ICAM-1 in late BSCB disruption after radiation.
Nordal
Robert A
RA
Department of Radiation Oncology, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
Wong
C Shun
CS
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000528:radiation effects; D015415:Biomarkers / Q000032:analysis; D001812:Blood-Brain Barrier / Q000502:physiology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism / Q000528:radiation effects; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects*
D000418:Albumins; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018799:Intercellular Adhesion Molecule-1