Intercellular Adhesion Molecule-1 and Blood-Spinal Cord Barrier Disruption in Central Nervous System Radiation Injury

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Abstract
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.

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