Validation of the model of neonatal status epilepticus for study of neurodevelopmental disorders

Abstract

Adult animals that have sustained neonatal lesions are increasingly considered useful models to study neurodevelopmental deficits underlying neuropsychiatric disorders such as schizophrenia and autism. Neonatal lesions are considered when ocurring between 8-10 days after birth, since this period corresponds to a full-term newborn. Status epilepticus (SE), an acute condition characterized by repetitive or prolonged seizures, occurs most often in children than in adults, and 40-50% of cases in children younger than two years. Although the immature brain is more susceptible to seizures than the mature ones, it has been assumed that this is less vulnerable to structural damage induced by status epilepticus (SE). However, experimental studies demonstrate that the neonatal SE may impair hippocampal-dependent memory, synaptic plasticity through alterations in inhibitory synaptic transmission and in glutamatergic synapse, modifies GABAergic intracortical circuitry, enhances apoptosis in the thalamus and reduces dopamine levels in the prefrontal cortex. We previously demonstrated that a single episode of neonatal SE in rats produces autistic behavior characterized by low preference by social novelty, social discrimination defict and anxiety related behavior, but the underlying mechanisms remain to be investigated. Some behavioral measures for validating the model have been used and the others are being proposed in this project. The main goal of this project is to search for evidence of the validity of neonatal SE model for the study of neurodevelopmental disorders. (AU)