Neurotoxicity of kainic acid in the rat cochlea during early developmental stages

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Abstract
The neurotoxic effect of kainic acid (KA) was investigated by electron microscopy in rat cochleas at two developmental stages: 17 days of gestation (17 G) and postnatal day 1 (PN 1). In each animal, one cochlea was injected with 1 nmol KA diluted into 2 ml artificial perilymph, while the other cochlea was only injected with artificial perilymph as a control. Ten minutes later, the cochleas were perfused with fixative, removed and processed for electron microscopy. The KA injection resulted in marked swelling of the majority of afferent fibers, i.e. the peripheral processes of spiral ganglion neurons. In the 17 G cochlea, swollen fibers were traced from the perikarya to the undifferentiated otocyst epithelium. Following birth, swollen afferents in the PN 1 cochlea were in contact with both inner (IHCs) and outer hair cells (OHCs), which were now differentiated. At both stages of development, a subclass of small afferent nerves were unaffected. At PN 1, the KA-insensitive afferents only contacted the OHCs. These fibers probably belong to the spiral system of afferents and are related to type II spiral ganglion cells. Conversely, KA-sensitive afferents probably belong to the radial system, related to type I spiral ganglion cells. This system is specific for IHCs in adult cochleas and appears to innervate both IHCs and OHCs at early developmental stages. These findings also indicate that KA neurotoxicity appears very early in the cochlea, at a prenatal time (17 G) before the presynaptic partners of afferent terminals (namely the IHCs) are differentiated. Thus, the neurotoxicity caused seems to be mediated via receptors located on the postsynaptic fiber and is widely distributed, as an immediate effect is visualized along the entire length of the unmyelinated peripheral afferent neurite.