The brain tissue samples of newborn infants suffering from hypoxic-ischemic insult in germinal matrix region: NF-kB/Parkin/ VEGFR-1 pathway

*Correspondence: [e-mail].

Abstract

Background: The hypoxic-ischemic insult is one of the current leading causes of neonatal deaths. The germinal matrix (GM) of the Central Nervous System (CNS) is a highly vascularized region susceptible to hemorrhagic damage in the face of a hypoxic environment. Considering the high activity of the GM until the thirty-sixth gestational week and its intrinsic link to hypoxemia and, consequently, neural damage with sequelae or death, investigating molecular pathways associated with the hypoxemic event is crucial to mitigate morbidity and mortality.

Objective: Therefore, the present study evaluated, throughout immunohistochemistry, cell survival markers (AKT-3, Parkin, and TRK-C), cell transcription (NF-kB), and angiogenic factor (VEGFR-1), to understand the connection of these markers in the GM and the hypoxic-ischemic insult of newborns.

Methods: The study comprised 118 post-mortem samples of a paraffin-embedded GM from premature and full-term patients who died within the first 28 days of life, divided into two groups related to CNS immaturity (extremely immature CNS and not immature CNS). Histopathological and immunohistochemical were used to analyze the AKT-3, NF-kB, Parkin, TRK-C, and VEGFR-1 markers in the conditions of asphyxia, prematurity, and death events within 24h.

Results: By evaluating the tissue immunoexpression of the markers in term and premature newborns, a possible molecular pathway was found with the interaction between the temporality of death within the first 24 hours and the transcription factor NF-kB and the angiogenic marker VEGFR-1, which were significantly decreased. Furthermore, there was an increase in tissue immunoexpression of NF-kB, AKT-3, and Parkin markers in the GM of prematurely aged patients.

Conclusion: Considering that the AKT-3 and Parkin markers showed a significantly increased, a high proliferative activity of GM and a possibility of protection against an ischemic insult is suggested. However, both NF-kB and its pro-cursor VEGFR-1 were significantly reduced compared to the survival time, proposing an insufficient time for the transcription and expression of VEGFR-1 in the plasmatic membrane, leading to a decreased protective activity. Therefore, this study is ongoing to identify a possible clinical marker in serum level to signal the ischemic hypoxic insult during the postpartum procedure, treating it as soon as possible.