Protocol for Drug Screening with Quantitative Video-Electroencephalography in a Translational Model of Refractory Neonatal Seizures

Abstract

The neonatal brain is more prone to seizures than the adult brain, with the highest incidence of seizures occurring during the first year of life. Neonatal seizures are the most common neurological emergency in newborns, occurring in 1–3.5 per 1000 newborns. The majority of neonatal seizures, chiefly those associated with hypoxic ischemic encephalopathy (HIE), are refractory to first-line anti-seizure medications (ASMs). The global first-line ASM for HIE neonatal seizures is phenobarbital (PB), a positive allosteric modulator of GABAA receptors (GABAARs). However, commonly used loading doses of PB are often ineffective for curbing HIE neonatal seizures. Without efficacious management strategies, poor seizure management devolves into prolonged and recurrent seizures associated with significant mortality, neurodevelopmental comorbidities, and epileptogenesis. The mechanisms underlying refractory neonatal seizures are poorly understood, as preclinical models that recapitulate important aspects of HIE historically have not been validated for their acute seizure burdens or ASM response quantitatively with video-electroencephalography (vEEG). In this chapter, we describe a protocol for drug screening with quantitative vEEG in a translationally sound model of refractory neonatal seizures.