Seizures are more common early in life than in adulthood. Bidirectional interactions between seizures and normal developmental processes define their expression and outcomes. Several developmentally regulated factors control neuronal excitability. GABAA
receptors hold a central role as they control neuronal activity in an age-specific manner. Early in development, GABAA
receptors have depolarizing effects, which contribute to the increased susceptibility of immature neurons to seizures but they are also essential for normal brain development. During development, there is a gradual shift to the "adult-type" hyperpolarizing GABAA
receptor signaling, creating more efficient inhibition. Seizures may disrupt GABAA receptor signaling by changing the expression of their subunits and by changing the direction of GABAA
responses, which, in certain situations, may be detrimental for brain development. Furthermore, subcortical nuclei, such as the substantia nigra, control the expression and propagation of seizures in an age- and sex-dependent manner. These endogenous control centers and signaling pathways are further modified by independent genetic epigenetic, biologic, or other factors, which further increase the heterogeneity in presentation of seizures, their treatment, and their comorbidities. Elucidation of these complex interactions and identification of biomarkers guiding therapeutic interventions will be necessary to improve our ability to treat early-life epilepsies.
Table of Contents
Seizures and Epilepsy: Definitions, Classification, Models
Brain Development Controls Seizure Susceptibility and Outcomes
About the Author(s)Aristea Galanopoulou
, Albert Einstein College Of Medicine
I received my MD degree from the National and Kapodistrian University of Athens, Greece. I completed my PhD in Experimental Medicine at McGill University, Montreal Canada, with Professor Yogesh C. Patel, MD PhD. My PhD studies aimed at elucidating the enzymes involved in the processing of the pro-hormone prosomatostatin to its active hormones. During my PhD, I became strongly interested in pursuing an academic career in Neurology. Following a year of internship in Medicine at Union Memorial Hospital in Baltimore, MD, I joined the Department of Neurology at the Albert Einstein College of Medicine where I completed my residency in Adult Neurology and the Clinical Neurophysiology fellowship. I have been at Einstein ever since, as faculty. My research interest is to unravel the mechanisms of early-life epileptogenesis and the interactions of early-life seizures and epilepsies on brain development. My early work revolved around the role of GABAA receptor signaling on brain development, its role as a broadcaster of sex- and age-specific signals that contribute to or alter brain development, and the manner in which early-life seizures affect this complex interaction between GABAA
and brain development. To obtain more tools to study early-life epileptogenesis, my research group, in collaboration with Solomon (Nico) L. Moshe, MD, have developed new animal models of early-life epileptic encephalopathies with infantile spasms that enabled us to proceed to preclinical studies for the identification of new treatments and to identify new putative targets for novel treatments. I am a member of the American Neurological Association, American Academy of Neurology, and the American Epilepsy Society. I have been invited to participate in committees assigned by the International League Against Epilepsy and the American Epilepsy Society to develop new guidelines for the preclinical drug development for epilepsy, as well as develop education programs that relate to epilepsy therapy and basic science. I am an editorial board member of the Neurobiology of Disease, Epilepsy Research, and Epilepsy Currents.