Dose optimization of NMDA for rat model of infantile spasms: Approach using EEG, behavior (Seizure) and histopathology

Abstract

Infantile Epileptic Spasms Syndrome (IESS), also referred to as West syndrome, is a severe epileptic disorder that emerges during early childhood. It is marked by characteristic epileptic spasms, developmental stagnation or regression, and a distinctive electroencephalogram (EEG) pattern known as hypsarrhythmia. To better understand the underlying mechanisms of IESS, various genetic and chemically induced animal models have been developed. Among these, the N-methyl-D-aspartate (NMDA) induced model is widely used, although it is often associated with high toxicity and mortality. In the study, we optimized the NMDA dose to reduce toxicity while maintaining the pathological features of IS. The validity of the model was assessed through EEG recordings, behavioural assessments, and brain histopathology. EEG analysis in the NMDA treated group revealed prominent abnormalities, including irregular wave patterns and elevated interictal activity. Histological examination showed signs of neuronal damage, such as nuclear pyknosis, in the model group. Behavioural tests assessing locomotion, memory, stereotypic activity, and anxiety like behaviour did not show significant differences between control and NMDA exposed rats. These findings demonstrate that a reduced and optimised dose of NMDA can reliably induce IS-like features in rats, offering a safer and effective model for future preclinical research.