Immunolocalization of endothelin in the traumatized spinal cord: relationship to blood-spinal cord barrier breakdown

The purpose of this study was to determine the relationship between endothelin-1 (ET-1), a prominent vasoactive agent, and the breakdown of the blood-spinal cord barrier along the axis of the cord after a moderate spinal cord injury. In the first study rats (n = 10) were euthanized 24 h after spinal cord injury and compared to sham (n = 5) and unoperated (n = 10) controls. Endothelin and immunoglobulins (IgG) were immunolocalized in adjacent sections of spinal cord using semiquantitative immunocytochemical techniques. In the second study animals were pretreated with the endothelin antagonist Bosentan (n = 6) or vehicle (n = 6) prior to spinal cord injury. Animals were euthanized at 24 h postinjury. Ten minutes prior to euthanasia animals were given horseradish peroxidase (HRP) intravenously. After perfusion fixation sections of cord were prepared for quantitative HRP histochemistry. After spinal cord injury there was enhanced staining for endothelin along the axis of the cord that correlated with the anatomical pattern of barrier breakdown to IgG. In those animals that were pretreated with Bosentan, there was a significant reduction in barrier breakdown along the axis of the injured cord as compared to those animals that received vehicle only. Taken together, this data implicate involvement of endothelin in the axial pattern of barrier breakdown after spinal cord injury.