Noise, Calpain, Calpain Inhibitors, and Neuroprotection: A Preliminary Report of Tinnitus Control

Frequently, noise-induced hearing loss is associated with the symptom of tinnitus. Preliminary results in the animal model after noise exposure suggest that the calpain inhibitor leupeptin may protect against noise-induced hearing loss. A final common pathway for cell destruction and cell death (i.e., apoptosis) is the calpain hypothesis. Calpain is a normal, intracellular, cytosolic protease activated by excess intracellular calcium. Calpain inhibitors (AK275, AK295) have been shown to provide neuroprotection in the central nervous system. A collaboration of basic science and clinical research efforts focusing on calpain antagonists and inhibitors was established in New York in 1997; the initiators are attempting to develop neuroprotective drug therapy regimens for hearing and balance system complaints, particularly hearing loss, tinnitus, and vertigo. Both calpain inhibitors and antagonists are being developed and are being investigated wth perfusion techniques of the inner ear, in vitro and in vivo, for their effects on peripheral and central portions of the cochleovestibular system.