Sodium nitroprusside/nitric oxide causes apoptosis in spiral ganglion cells

In the cochlea, excitatory amino acid receptor overstimulation induces toxicity in spiral ganglion neurons by an unknown mechanism. In the central nervous system, excitatory amino acid-induced toxicity is mediated by nitric oxide, which induces apoptosis in neurons. This study tested the hypothesis that cochlear nitric oxide-mediated toxicity is the result of induction of apoptosis in spiral ganglion neurons.

The cochleas of 15 gerbils randomly assigned to different groups were perfused for 30 minutes with a test solution of 1 mmol/L sodium nitroprusside, a nitric oxide donor, or a control solution of artificial perilymph. Animals were killed at varying times, including 2, 3, 4, 8, and 18 hours after perfusion. DNA fragmentation or in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling analysis was done on cochleas for detection of apoptosis.

Analysis by both techniques demonstrated marked apoptotic cell changes in spiral ganglion neurons of sodium nitroprusside-treated cochleas evident 4 to 8 hours after perfusion, as compared with minimal to no evidence of apoptosis in spiral ganglion neurons of control specimens.

Exposure to high levels of nitric oxide induces apoptosis in spiral ganglion neurons. Because apoptosis is a delayed, potentially reversible cell death pathway, this may present an opportunity for intervention to prevent or attenuate hearing damage induced by excitotoxic stimuli.