Treatment of status epilepticus (SE) in infants and children is challenging. There is a recognition that a broad set of developmental processes need to be considered to fully appreciate the physiologic complexity of severe seizures, and seizure outcomes, in infants and children. The development and use of basic models to elucidate important mechanisms will help further our understanding of these processes. Here we review some of the key experimental models and consider several areas relevant to treatment that could lead to productive translational research. Terminating seizures quickly is essential. Understanding pharmacoresistance of SE as it relates to receptor trafficking will be critical to seizure termination. Once a severe seizure is terminated, how will the developing brain respond? Basic studies suggest that there are important acute and long-term histopathologic, and pathophysiologic, consequences that, if left unaddressed, will produce long-lasting deficits on the form and function of the central nervous system. To fully utilize the evidence that basic models produce, age- and development- and model-specific frameworks have to be considered carefully. Studies have demonstrated that severe seizures can cause perturbations to developmental processes during critical periods of development that lead to life-long deficits. Unfortunately, some of the drugs that are commonly used to treat seizures may also produce negative outcomes by enhancing Cl--mediated depolarization, or by accelerating programmed cell death. More research is needed to understand these phenomena and their relevance to the human condition, and to develop rational drugs that protect the developing brain from severe seizures to the fullest extent possible.

During flurothyl seizures in 4-day-old rats, cortical concentration of ATP, phosphocreatine and glucose fell while lactate rose. Cortical energy use rate more than doubled, while glycolytic rate increased fivefold. Calculation of the cerebral metabolic balance during sustained seizures suggests that energy balance could be maintained in hyperglycemic animals, and would decline slowly in normoglycemia, but would be compromised by concurrent hypoglycemia, hyperthermia or hypoxia. These results suggest that the metabolic challenge imposed on the brain by this model of experimental neonatal seizures is milder than that seen at older ages, but can become critical when associated with other types of metabolic stress.