Modern neurochemical and molecular genetic aspects of the pathogenesis of neonatal seizures

Abstract

The article is devoted to the modern aspects of the pathogenesis of neonatal seizures (NS). The main mechanisms of the development of perinatal brain injuries, which are fundamental in the genesis of NS, are considered, the prospects for research devoted to the study of the possibilities of molecular genetic prediction of the individual risk of ischemia and the development of NS are outlined. The mechanisms of ischemic brain damage during the neonatal period and the role of glutamate, the main excitatory neurotransmitter acting on NMDA receptors that regulate the electrical activity of neurons, are described in detail. The review focuses on the involvement of metalloproteinases, primarily MMP-9, which destroys type IV collagen, which is the main component of the basement membrane of the cerebral endothelium, and creates conditions for cell migration across the BBB, thereby causing a cytokine storm and the development of inflammation, leading to NS. The possible role of calcium-dependent proteinases — calpains in the development of NS is analyzed, since in some forms of CNS pathology, uncontrolled hyperactivation of calpains is observed, leading to a disruption of the regulation of neurotransmitter transmission, which can, in turn, become an additional factor for the development of the neurodegenerative process in the brain and the development of seizures. Also are presented the results of studies devoted to the role of ion channels, providing synaptic transmission of excitation from an excited neuron to other cells. It has been shown that molecular defects in ion channels can be one of the factors that create prerequisites for the development of NS. The article shows the prospects for studying the genetic polymorphism of enzymes involved in the pathogenesis of ischemic brain damage, based on ideas about the pathogenesis of cerebral disorders in newborns, which are based on oxidative damage. The concluding part of the article outlines the modern principles of NS therapy, their main goal is to relieve the symptoms of the underlying disease, to ensure the normalization of blood circulation and brain metabolism, to optimize the conditions for the functioning of the preserved brain structures to prevent the formation of severe neurological complications, as well as to maintain optimal parameters of respiration, glucose-electrolyte composition of blood and thermal regime. Based on the data presented, it is concluded that early diagnosis of NS is necessary, which is determined by the fact that seizures in newborns are usually caused by serious damage to the child's brain, and in some cases — by life-threatening conditions, the timely diagnosis of which contributes to the early onset of specific treatment.