Systems approach to the study of brain damage in the very preterm newborn

Abstract

Background: A systems approach to the study of brain damage in very preterm newborns has been lacking.Methods: In this perspective piece, we offer encephalopathy of prematurity as an example of the complexity and interrelatedness of brain-damaging molecular processes that can be initiated inflammatory phenomena.Results: Using three transcription factors, nuclear factor-kappa B (NF-κB), Notch-1, and nuclear factor erythroid 2 related factor 2 (NRF2), we show the inter-connectedness of signaling pathways activated by some antecedents of encephalopathy of prematurity.Conclusions: We hope that as biomarkers of exposures and processes leading to brain damage in the most immature newborns become more readily available, those who apply a systems approach to the study of neuroscience can be persuaded to study the pathogenesis of brain disorders in the very preterm newborn.

Microorganisms in the human placenta are associated with altered CpG methylation of immune and inflammation-related genes

“…It has been shown that bacterial plasmid DNA activates a signaling cascade that leads to activation of the NF-κB pathway and expression of inflammatory genes [ 31 ]. There is also accumulating evidence that NF-κB activity increases with the onset of labour [ 32 , 33 ] and is tied to children’s health later in life [ 34 ]. Of the five NF-κB genes that were differentially methylated, four are known to induce NF-κB signaling.…”

Measuring Cot-Side the Effects of Parenteral Nutrition on Preterm Cortical Function

“…The rationale starts from the well-established, intimate structurefunction link where rapid structural maturation of brain circuitry is guided and driven by endogenous neuronal activity (Vanhatalo and Kaila, 2006;Hanganu-Opatz, 2010;Luhmann et al, 2016;Keunen et al, 2017;Khazipov and Milh, 2018). There is also an increasing awareness of the sensitivity of early neuronal network activity to a variety of stress factors ranging from metabolic imbalance, such as nutritional stress, medical adversities and medical treatments (Keunen et al, 2015;Leviton et al, 2015;Videman et al, 2016Videman et al, , 2017.…”

Современные Возможности Идентификации Новых Молекул-Мишеней Для Фармакологической Коррекции Проницаемости Гематоэнцефалического Барьера

“…Ó÷èòûâàÿ ïðîâîñïàëèòåëüíûé ýôôåêò NF-kB, ýòîò ñèãíàëüíûé ïóòü ìîaeíî ðàññìàòðèâàòü êàê ìèøåíü äëÿ ðåãóëÿöèè ïðîíèöàåìîñòè ÃÝÁ [44]. Äîêàçàíî, ÷òî àêòèâàöèÿ NF-kB ïðîèñõîäèò íå òîëüêî ïîä âëèÿíèåì HIF-1 â óñ-ëîâèÿõ ãèïîêñèè, íî è ïðè äåéñòâèè ëèïîïîëèñàõàðè-äîâ.…”