Reversible and irreversible damage to cochlear afferent neurons by kainic acid excitotoxicity

Kainic acid (KA) selectively damages afferent synapses that innervate, in c hickens, mainly tall hair cells. To better understand the nature of KA-indu ced excitotoxic damage to the cochlear afferent neurons, KA, at two differe nt concentrations (0.3 or 5 mM), was injected directly into the inner ear o f adult chickens. Pathologic changes in the afferent nerve ending and cell body were evaluated with light and transmission electron microscopy at vari ous time points after KA application. The compound action potential (CAP) a nd cochlear microphonic (CM) potential were recorded to monitor the physiol ogic status of the afferent neurons and hair cells, respectively. Hair cell morphology and function were essentially normal after KA treatment. Howeve r, afferent synapses beneath tall hair cells were swollen within 30 minutes after KA at both low (KA-L) and high (KA-H) doses. In the KA-L group, the swelling disappeared within 1 day and the morphology of the postsynaptic re gion returned to near normal condition. In the KA-H group, by contrast, the vacant region beneath tall hair cells remained evident even 20 weeks after KA. The number of cochlear ganglion neurons in the KA-H group decreased pr ogressively from 1 to 8-20 weeks, whereas hair cells in the basilar papilla remained morphologically intact out to 20 weeks after KA. There was no sig nificant change in neuron number in the KA-L group. Temporal changes in the CAP amplitude paralleled the anatomic changes, although the CAP only parti ally recovered. These results suggest that KA induces partially reversible damage to cochlear afferent neurons with low KA concentration; above this l evel, KA triggers irreversible, progressive neurodegeneration. J. Comp. Neu rol. 430:172-181, 2001. (C) 2001 Wiley-Liss, Inc.