SPINAL ENDOTHELIN CONTENT IS ELEVATED AFTER MODERATE LOCAL TRAUMA IN THE RAT TO LEVELS ASSOCIATED WITH LOCOMOTOR DYSFUNCTION AFTER INTRATHECAL INJECTION

The role of endothelin (ET) in the pathophysiology of secondary neural damage after experimental spinal cord injury (SCI) was examined in a rat model of weight-drop contusion injury. Initial studies demonstrate d a significant increase in spinal ET concentrations in a 7.5-mm segme nt of tissue (centered at the impact site) at 30 min, 4 h, and 24 h af ter a moderate (50 g-cm) contusion injury, Subsequent experiments were aimed at reproducing these elevations by the intrathecal (i.t.) admin istration of ET and observing the effect on locomotor function, These studies showed that i.t. dosage of 9.6 ng produced spinal cord elevati ons of ET similar to those seen 30 min after moderate SCI as well as m ild locomotor deficits, A 48 ng dose of ET resulted in moderate to sev ere locomotor deficits that were associated with spinal ET elevations much greater than those seen after injury, The mild deficits attributa ble to the lower dose of ET could contribute to the pathophysiological actions of other purported secondary injury mediators, The more prono unced locomotor deficits associated with the higher dose could be of r elevance for severe SCI.