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AN INDIRECT PATHWAY FOR GENETIC INFLUENCE ON THE FORMATION OF THE CEREBRAL PALSY PHENOTYPE: GENOME AND HYPOXIA TOLERANCE


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Abstract

The incidence of cerebral palsy is increasing. In 70% of cases, the disease develops as a result of exposure to known pathogenesis factors, such as hypoxia-ischemia, infectious, toxic, and traumatic damage to the fetus. In 30% of cases of the disease, the effect of pathogenetic factors is absent. This determines the relevance of the search for genetic anomalies responsible for the formation of this phenotype. Many genome disorders associated with the development of the cerebral palsy phenotype have been identified. Of particular interest is the indirect influence of genetic factors of pathogenesis, affecting the formation of the disease indirectly, through the mechanisms of formation of hypoxic-ischemic brain damage. Such factors affect almost all stages of the “ischemic cascade”: the formation of a “glutamate shock”, the realization of a “glutamate shock” by cytokines, the defect of the antioxidant defense of a neuron, the realization of the cytotoxic effect of nitric oxide (NO), and the stimulation of apoptosis of neurons and microglia. This makes it possible to identify genome variants that determine the tolerance of the child’s brain to hypoxic-ischemic damage. The combination of carriers of such anomalies into risk groups will make it possible to differentiate the tactics of their observation in the natal and postnatal periods in order to reduce the likelihood of the formation of severe hypoxic-ischemic lesions of the central nervous system and cerebral palsy. Today, a large amount of scientific data has been accumulated on the molecular genetic mechanisms of the pathogenesis of perinatal brain lesions. Such as epigenetic, transcriptome gene expression control mechanisms via micro-RNA. The available information allows us to experimentally develop new methods for protecting the fetal brain from hypoxia-ischemia and stopping the effects of hypoxia-ischemia in the neonatal period.


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