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Recent progress has been made regarding the prevention of hearing loss. However, the complete protection of both hair cells and spiral ganglion neurons, with restored function, has not yet been achieved. It has been shown that spiral ganglion neuronal loss can be prevented by neurotrophin 3 (NT3) and hair cell damage by N-methyl-D-aspartate (NMDA) receptor antagonists. Here we demonstrate that the combined treatment with MK801, a NMDA antagonist, and NT3 protect both cochlear morphology and physiology from injury. Pretreatment with MK801 prevented hearing loss and the dendrites of the spiral ganglion neurons from swelling after noise-induced damage. The acute phase of insult with the aminoglycoside antibiotic amikacin resulted in swollen afferent dendrites beneath the inner hair cells. The chronic phase resulted in complete hair cell loss and near-complete loss of spiral ganglion neurons. This damage caused a near-complete loss of hearing sensitivity as displayed by elevated (>90-dB sound pressure levels) auditory brainstem response thresholds. The treatment of amikacin-exposed animals with MK801 gave only a partial protection of hearing. However, the combined treatment with NT3 and MK801 in the amikacin-comprised ear resulted in improved mean hearing within 20 dB of normal. Furthermore, hair cell loss was prevented in these animals and spiral ganglion neurons were completely protected. These results suggest that the NMDA antagonist MK801 protects against noise-induced excitotoxicity in the cochlea whereas the combined treatment of NT3 and MK801 has a potent effect on preserving both auditory physiology and morphology against aminoglycoside toxicity. O ne in 10 individuals is affected by hearing disorders. Hearing impairments can be caused by a variety of factors including noise, ototoxic substances such as aminoglycosides, and aging. These factors affect the hair cells in the mammalian organ of Corti that transduce auditory signals to the brain via the spiral ganglion neurons. Hearing deficiencies are caused by loss of hair cells or spiral ganglion neurons and these changes are often permanent. Sensory neurons and hair cells are not capable of postembryonic cellular mitosis to produce new hair cells and neurons. It is therefore necessary to develop pharmacological strategies aimed at preventing or repairing damaged hair cells or spiral ganglion neurons.The most important afferent neurotransmitter in the peripheral auditory system is the excitatory amino acid glutamate (1, 2). When glutamate is released from the inner hair cells it binds to N-methyl-D-aspartate (NMDA) receptors located on the terminals of the spiral ganglion neurons. NMDA receptors are expressed in the auditory neurons and little or no mRNA for the receptor subunits has been detected in other areas of the cochlea (3). It has been shown that NMDA receptors play a key role in excitotoxic cell death after ischemic, stroke, hypoglycemia, alcohol intoxication, and epilepsy (4). Cell death caused by excitotoxicity has been suggested to be caused by cy...

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In the 285 patients with cranial complications, 253 had a single complication, 29 had two complications, and 3 had more than two complications. Intracranial complications included meningitis (16 cases), brain abscess (42 cases), sigmoid sinus involvement (29 cases), extradural abscess (8 cases), subdural abscess (1 case), and hydrocephalus (2 cases). Extracranial complications included labyrinthitis (90 cases), mastoid abscess (79 cases), facial paralysis (47 cases), Bezold abscess (5 cases), and apicitis pyramidalis (1 case). In all, 267 patients were cured or improved without recurrence. Five patients died from complications, of whom four died of cerebral hernia and one died of multiple abscesses.