DYNORPHIN NEUROTOXICITY INDUCED NITRIC-OXIDE SYNTHASE EXPRESSION IN VENTRAL HORN CELLS OF RAT SPINAL-CORD

Nitric oxide (NO) mediation in the spinal cord injury induced by intra thecal (i.t.) dynorphin (Dyn) administration was studied with NADPH-di aphorase (Nd) histochemistry. Normally, there was rarely NO synthase ( NOS) activity in spinal cord motoneurons, and Dyn A(1-17) 10 nmol, whi ch produced only transient paralysis, did not induce Nd/NOS expression in ventral horn cells. After a paralyzing dose of i.t. Dyn A(1-17) 20 nmol, which definitely produced permanent paraplegia and neuronal dea th, Nd/NOS began to express in motoneurons at 30 min, increased in num bers and intensities at 2-4 h and persisted up to 8 h. Most of Nd/NOS motoneurons disappeared at 24 h coincident with the neuronal death. Qu ite a few intensively-stained Nd-positive small cells and swollen vari cosities became visible only in rats with permanent paraplegia and neu ronal death, beginning at 2 h, maximizing at 3-4 h and remaining up to 24 h. These results suggest that NOS expression was induced in the ve ntral horn of spinal cord, including small cells and varicosities as w ell as motoneurons closely correlated in time and degree with patholog ical changes in motoneurons caused by spinal Dyn neurotoxicity.