The Mechanisms of Stress in Epileptogenesis

Epileptogenesis is a gradual, multifaceted pathological process in which the brain undergoes structural and/or functional changes that ultimately culminate in the onset of spontaneous seizures. This process is driven by a range of biological and environmental influences. Growing evidence indicates that stress is a major risk factor for epileptogenesis, amplifying neural hyperexcitability and seizure susceptibility through multiple neurobiological pathways, including hyperactivation of the hypothalamic-pituitary-adrenal axis, disruption of neurogenesis and circuit remodeling, excitatory–inhibitory imbalance, and neuroinflammatory responses. The pediatric period represents a uniquely vulnerable stage of development in which the brain is particularly sensitive to such stress-induced changes. Early exposure to stress during this critical window may produce enduring alterations that heighten the risk of chronic epilepsy. This review consolidates current knowledge on the principal pathophysiological mechanisms through which stress influences epileptogenesis, emphasizing childhood vulnerability and the resulting implications for clinical intervention. These insights may guide the development of novel therapeutic and preventive strategies tailored to early-life susceptibility.