Executive Summary : | Infantile spasm (Is), also known as West syndrome, is a rare and devastating epileptic encephalopathy (EE) characterized by epileptic spasms, psychomotor stagnation, and hypsarrhythmia. It occurs in the first year of life and has a peak between 4 and 7 months, resulting in poor neurological and behavioral outcomes. Despite extensive pharmacological treatment, affected patients suffer from ongoing seizures and cognitive dysfunction. The pathophysiology of Is is still not fully understood, with research focusing on understanding the underlying mechanisms, identifying new therapeutic targets, improving diagnostic methods, and evaluating the effectiveness of different treatment approaches. Excitotoxicity, a pathological process characterized by excessive activation of glutamate receptors, plays a crucial role in the development and progression of Is. N-methyl-D-aspartate receptor (NMDAR) dysfunction is implicated in a range of neuropsychiatric disorders, including epilepsy. A preclinical animal model of Is involves prenatal exposure of betamethasone and postnatal exposure of the glutamate receptor agonist NMDA, which triggers the activation of glutamate receptors, ultimately inducing flexion spasms. studies have shown that NMDAR antagonist, memantine, and a negative allosteric modulator of one subunit of NMDA receptor, Radiprodil, have anti-epileptic effects in Is. In vitro studies have shown that IGF-1 treatment can reduce NMDA-induced excitotoxity in hippocampal neurons via the MAPK/ERK pathway. This project proposes reducing excitotoxicity involved in Is pathogenesis by administering NMDAR antagonist, Amantadine, and IGF-1 analogue, long arginine 3-IGF-1 (LR3 IGF-1) individually and in combination in the NMDA-induced animal model of Is. |