Excitotoxic lesion in the corpus callosum of neonatal rats: A model for encephalopathy of prematurity.

Abstract

Encephalopathy of prematurity (EP) can develop in preterm infants exposed to risk factors like extreme prematurity, low birth weight, hypoxia, infections, and inflammation. These factors can induce excitotoxicity in the brain's gray and white matter, leading to the death of neurons and oligodendrocyte progenitors. Understanding the brain mechanisms of EP requires animal models. In this study, we generated an EP model by injecting N-methyl-D-aspartic acid (NMDA) into the corpus callosum (CC) of neonatal male rats on postnatal day (PND) 5. Rats were divided into five groups: Intact, Vehicle, and three doses of NMDA (3, 4, or 5 μg). On PND 20, we measured the volumes of the CC, motor cortex (MC), and lateral ventricles. The 5 µg NMDA dose caused the largest lesion. We later assessed these structures on PNDs 6, 10, 20, and 30 to monitor lesion progression. We also analyzed myelin basic protein (MBP) expression and counted NeuN-positive cells using immunofluorescent markers. NMDA groups showed reduced MBP expression and fewer NeuN-positive cells in the MC. Additionally, NMDA-treated rats exhibited increased motor activity in the open field and reduced fall latencies in the rotarod task compared to controls. In conclusion, our perinatal excitotoxic lesion model in rats demonstrates structural abnormalities, including decreased MBP and loss of NeuN-positive cells, alongside motor and habituation impairments, resembling those seen in human EP.