Perinatal hipoxic ischemic injury in the auditory pathway and the effect of several neuroprotective agents

Abstract

Despite improvements in neonatology, perinatal hypoxic-ischemic (HI) encephalopathy remains one of the main causes of disabilities in term-born infants. This specific pathology underlies many neurological disorders such as learning difficulties, language and attention deficit, hyperactivity disorders and cerebral palsy. Moreover, it is also a notable risk factor for hearing impairments which affect neonates.Insult from hypoxia-ischemia causes immediate neuronal injury and exhaustion of cellular energy stores, as the main cause of HI brain injury is the deprivation of glucose and oxygen supply, which initiates a multi-faceted cascade of biochemical events. The combined effects of cellular energy failure, acidosis, glutamate release, intracellular calcium accumulation, lipid peroxidation, and nitric oxide neurotoxicity provoke, in many cases, the death of the cells, either by necrosis or apoptosis, a divergence that will depend on the severity of the insult, the maturational state of the cell or the brain region affected, among others. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury.The aim of this work is to evaluate with morphofunctional, molecular and cellular methods the effect of a panel of antioxidants on HI-induced auditory deficits. To this end, we studied the effects of Nicotine, Melatonin, Resveratrol and DHA on the neonatal auditory system via measurement of auditory evoked potentials and characterization of the morphological, molecular and cellular integrity of the IC.