Molecular approach of hypoxic-ischemic encephalopathy and its consequences in preterm infants

Abstract

Hypoxic-ischemic encephalopathy (HIE) is the most serious consequence of perinatal asphyxia and the most common cause of seizures in infants, accounting for 60% to 65% of the cases, both in term newborns (TN) and in preterm infants (PN), being an important factor of neurological sequelae. Intracranial hemorrhage (ICH) and periventricular leukomalacia (PVL) is the most common brain disorders of preterm infants. The PVL is a degeneration of the cerebral white part caused by several factors, especially after severe deprivation of oxygen in preterm infants. Although a number of changes in genes that may be of importance in the etiology of PVL, few studies have been conducted in Brazil. Experimental studies indicate that inflammation is involved in the pathogenesis of PVL. The inflammatory cascade triggered by ischemia in the central nervous system consists of large influx of leukocytes at the site, which include neutrophils, monocytes and macrophages. Thus, the neuropathological feature of PVL is a large concentration of activated microglia and other macrophages that produce proinflammatory cytokines, which may directly cause oligodendroglial cell death or exacerbate white matter lesions, contributing to the pathophysiology of perinatal brain injury, in the genesis of PVL and subsequent clinical manifestations. This study aims to investigate the possible association between polymorphisms (by technical PCR / RFLP)-1031T/C in TNF-alfa gene, -511C/T in IL-1beta and-1082G/A gene on IL-10 gene and the etiopathogenesis of PVL in premature newborns with HIE. Factors associated with persistent infection and disease progression are still not completely understood, although there is evidence that the host immune response affects the susceptibility to injury and its progression. The results will determine the frequency of these polymorphisms in the study sample, thus determining the allelic and genotypic frequency and perform comparative statistical study of the literature. Furthermore, they may contribute to better understanding of the molecular process of HIE, especially PVL. (AU)