Toxicology
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Aminoglycosides are bactericidal aminoglycosidic aminocyclitols. They are cost effective and therefore widely used, however ototoxicity is a prominent dose-limiting side effect. Aminoglycoside induced ototoxicity leads to permanent bilaterally severe, high-frequency sensorineural hearing loss and temporary vestibular hypofunction. ⋯ The development of aminoglycoside otoprotective strategies is a primary goal in ototoxicity research. Animal experiments have provided encouraging evidence for the protection of cochlear hair cells and neurons from aminoglycoside toxicity. However, the extent to which such protection, generalize to human ototoxicity remains unresolved.
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Ketamine, an anaesthetic agent used in newborns and toddlers, has been shown to induce neurodegeneration and alter adult behavior in mice, when administered during the neonatal period. Mammals have a marked period of rapid brain growth and development (BGS), which is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching its peak around postnatal day 10. CaMKII and GAP-43 play important roles during the BGS in mammals. ⋯ GAP-43 showed a significant increase in hippocampus, but a significant decrease in cortex for the highest ketamine dose. When looking at the adult behavior it was clear that neonatal ketamine exposure affected spontaneous behavior and habituation in a dose-response-related manner and that these behavioral disturbances were not transient but still persisted 2 months later. Taken together, this shows that ketamine affects important proteins involved in normal maturation of the brain and induce functional deficits in the adult individual, which further strengthen our findings concerning ketamine as a developmental neurotoxicological agent.