The Developing Brain and Neonatal Seizures: Neuroanatomical and Neurophysiological Mechanisms of Seizure Susceptibility
Ilija Palić1*, Olgica Rakić1
1Institute of Neonatology, Belgrade, Serbia.
*Corresponding Author: Ilija Palić, Institute of Neonatology, Belgrade, Serbia.
https://doi.org/10.58624/SVOAPD.2026.05.033
Received: September 01, 2026
Published: September 30, 2026
Citation: Palić I, Rakić O. The Developing Brain and Neonatal Seizures: Neuroanatomical and Neurophysiological Mechanisms of Seizure Susceptibility. SVOA Paediatrics 2026, 5:5, 218-233. doi: 10.58624/SVOAPD.2026.05.033
Abstract
Neonatal seizures represent a distinctive manifestation of neurological dysfunction arising within a rapidly developing and highly excitable brain. Their increased occurrence during the neonatal period reflects not only the high incidence of acute cerebral insults but also unique neuroanatomical and neurophysiological characteristics of immature neuronal networks. Transient cortical structures, evolving thalamocortical and corticocortical connectivity, intense synaptogenesis, and incomplete myelination provide a developmental substrate fundamentally different from that of the mature brain. At the cellular level, developmental regulation of GABAergic and glutamatergic neurotransmission, chloride homeostasis, voltage-gated ion channels, and excitatory–inhibitory balance contributes to enhanced neuronal excitability. These intrinsic characteristics interact with disturbances of cerebral energy metabolism, ionic gradients, and neuroinflammatory pathways following hypoxic–ischemic injury, perinatal arterial ischemic stroke, intracranial hemorrhage, infection, metabolic abnormalities, and structural brain disorders. The convergence of developmental susceptibility and superimposed cerebral pathology facilitates the transition from neuronal hyperexcitability to pathological synchronization and recruitment of immature neuronal networks. This review summarizes the neuroanatomical and neurophysiological foundations of neonatal seizure susceptibility and integrates them with the major pathophysiological mechanisms through which cerebral injury promotes seizure generation and propagation. Understanding neonatal seizures within this developmental framework provides a mechanistic perspective on why the immature brain is uniquely vulnerable to seizure activity.
Keywords: Neonatal Seizures; Developing Brain; Neuroanatomy; Neurophysiology; Brain Maturation; Neuronal Hyperexcitability