SB209670, A POTENT ENDOTHELIN RECEPTOR ANTAGONIST, PREVENTS OR DELAYSAXONAL DEGENERATION AFTER SPINAL-CORD INJURY

We developed a rat spinal cord transection injury model and investigat ed whether endogenous endothelin takes part in axonal degeneration aft er injury, by using a potent nonselective endothelin receptor antagoni st, SB209670. Light microscopic analysis showed that axonal degenerati on of the spinal cord was clearly observed one week after injury, supp orted by immunohistochemical study with anti-neurofilament antibody. E lectron microscopic observation showed enlargement and shrinking of sp inal axons in the injured sites one week after injury. Application of SB209670 to the lesion sites markedly inhibited axonal damage after in jury. These results suggest that endogenous endothelin plays a role in axonal degeneration after spinal cord injury and that SB209670 preven ts or delays the axonal degeneration after CNS damage. (C) 1998 Elsevi er Science B.V.