Cochlear integrity in rats with experimentally induced audiogenic seizure susceptibility.
While chronic susceptibility of rodents to audiogenic seizures (AGSs) is often accompanied by cochlear lesions, it has not been demonstrated whether cochlear hair cell losses are essential to pathogenesis in this epileptic disorder. An alternative possibility is that the neonatal timing of hearing losses is what unites various models of chronic AGS susceptibility. In the latter case, either transient or permanent hearing losses might induce susceptibility as long as they concur with a critical period of development. To address this issue, it was examined whether lesions were universally present in cochleas of adult rats after having been made susceptible to sound-triggered seizures by different types and severities of neonatal auditory trauma. Neonatal treatments included: (1) an 8 min exposure of rat pups to intense noise (125 dB SPL) on postnatal day (PND) 14; (2) injections of low doses of kanamycin (KM: 100 mg/kg) on PNDs 9-12; or (3) injections of high doses of KM (500 mg/kg) on PNDs 9-12. As adults, rats in all experimental groups, but not in sham-treated groups, exhibited sound-triggerable seizure responses. Nonetheless, this outcome did not depend on integrity of cochleas. Hair cells were rarely missing in the cochleas of noise-exposed, low-dosage KM-treated, or sham-treated rats. By contrast, all inner and outer hair cells were missing from the basal 75% of cochleas of adult rats which had been treated with high-dose KM on PNDs 9-12. Results indicate that cochlear lesions are not requisite for the induction or expression of AGS susceptibility. At the same time, however, significant hair cell losses do not necessarily preclude susceptibility. It appears that the neonatal timing rather than the permanence of hearing losses may be what engenders chronic AGS susceptibility.
Pierson
M
M
Cain Foundation Laboratories, Texas Children's Hospital (MC-3-6365), Baylor College of Medicine, Houston 77030, USA.
Li
D
D
D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity; D003051:Cochlea / Q000166:cytology / Q000187:drug effects / Q000293:injuries*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000503:physiopathology*; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000209:etiology / Q000503:physiopathology; D007612:Kanamycin / Q000008:administration & dosage / Q000633:toxicity; D009622:Noise / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis
D000900:Anti-Bacterial Agents; D007612:Kanamycin