INTRATHECAL ADMINISTRATION OF ENDOTHELIN-1 IN THE RAT - IMPACT ON SPINAL-CORD BLOOD-FLOW AND THE BLOOD-SPINAL CORD BARRIER

The purpose of this study was to examine the integrity of the blood-sp inal cord barrier after intrathecal administration of endothelin-1 (ET -1) in the rat spinal cord. A laser Doppler probe was positioned in th e exposed subarachnoid space at the T8 vertebral level. In the first e xperiment, horseradish peroxidase (HRP), a marker of barrier integrity , was given intravenously prior to the intrathecal application of ET-1 . Blood flow was then recorded for 3 h, after which the anesthetized a nimals were euthanized. In the second experiment, animals exposed to e ndothelin were recovered after confirming a 50% reduction in blood flo w. HRP was given 10 min prior to euthanasia at 24 h post infusion. The intensity of staining for HRP was quantified by optical density in fi xed sections of spinal cord. There was a significant sustained reducti on in spinal cord blood flow and significant barrier breakdown to HRP at both 3 and 24 h after administration of the peptide. Based upon the se results we conclude that intrathecal infusion of ET-1 reduces spina l cord blood flow and results in prolonged breakdown of the blood-spin al cord barrier.