Mechanisms and effects of seizures in the immature brain

• Published in: Seminars in fetal & neonatal medicine Vol. 18; no. 4; pp. 175 - 184
• Main Authors: Nardou, Romain, Ferrari, Diana C, Ben-Ari, Yehezkel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2013
• Subjects: Animals; Brain - metabolism; Brain - pathology; Child; Child Development; Child, Preschool; Disease Models, Animal; Disease Susceptibility; Epilepsy - metabolism; Epilepsy - physiopathology; Excitation/inhibition; Humans; Immature brain; Infant; Infant, Newborn; KCC2; Models, Biological; Neonatal and Perinatal Medicine; Neonatal seizures; Neurogenesis; Neurons - metabolism; Neurons - pathology; NKCC1; Seizures - metabolism; Seizures - physiopathology; γ-Aminobutyric acid; Immature brain; Neonatal seizures; γ-Aminobutyric acid; NKCC1; KCC2; Excitation/inhibition
• ISSN: 1744-165X; 1878-0946
• DOI: 10.1016/j.siny.2013.02.003

Summary The developing immature brain is not simply a small adult brain but rather possesses unique physiological properties. These include neuronal ionic currents that differ markedly from those in the adult brain, typically being longer-lasting and less selective. This enables immature heterogeneous neurons to connect and fire together but at the same time, along with other features may contribute to the enhanced propensity of the developing brain to become epileptic. Indeed, immature neurons tend to readily synchronize and thus generate seizures. Here, we review the differences between the immature and adult brain, with particular focus on the developmental sequence of γ-Aminobutyric acid that excites immature neurons while being inhibitory in the normal adult brain. We review the mechanisms underlying the developmental changes to intracellular chloride levels, as well as how epileptiform activity can drive pathologic changes to chloride balance in the brain. We show that regulation of intracellular chloride is one important factor that underlies both the ease with which seizures can be generated and the facilitation of further seizures. We stress in particular the importance of understanding normal developmental sequences and how they are interrupted by seizures and other insults, and how this knowledge has led to the identification of potential novel treatments for conditions such as neonatal seizures.