Impact of perinatal hypoxia on the developing brain

Abstract

Perinatal hypoxia is still one of the greatest threats to the newborn child, even in developed countries. However, there is a lack of works which summarize up-to-date information about that huge topic. Our review covers a broader spectrum of recent results from studies on mechanisms leading to hypoxia-induced injury. It also resumes possible primary causes and observed behavioral outcomes of perinatal hypoxia. In this review, we recognize two types of hypoxia, according to the localization of its primary cause: environmental and placental. Later we analyze possible pathways of prenatal hypoxia-induced injury including gene expression changes, glutaminergic excitatory damage (and a role of NMDA receptors in it), oxidative stress with ROS and RNS production, inflammation and apoptosis. Moreover, we focus on the impact of these pathophysiological changes on the structure and development of the brain, especially on its regions: corpus striatum and hippocampus. These brain changes of the offspring lead to impairments in their postnatal growth and sensorimotor development, and in their motor functions, activity, emotionality and learning ability in adulthood. Later we compare various animal models used to investigate the impact of prenatal and postnatal injury (hypoxic, ischemic or combinatory) on living organisms, and show their advantages and limitations.

Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases

“…Motor disabilities and memory damage Golan et al, 2004 executive functioning disorder and object recognition disorder (Delcour et al, 2012a;Smith et al, 2016;Piesova and Mach, 2020). In animal models, the effects of hypoxia on behavior are similar to those of ADHD.…”

“…In animal models, the effects of hypoxia on behavior are similar to those of ADHD. Animals often exhibit motor and learning disabilities, hyperactivity disorder, and decreased memory, socialization, and attention (Piesova and Mach, 2020).…”

“…The whole process of pregnancy and delivery is critical for the healthy development of the fetus. Therefore, limited oxygen supply (hypoxia) during pregnancy remains one of the greatest threats to fetal development ( Piesova and Mach, 2020 ). The overall incidence of fetal hypoxia varies greatly among European hospitals, ranging from 0.06 to 2.8% ( Giannopoulou et al, 2018 ).…”

“…Prenatal hypoxia can have adverse effects on the development of the central nervous system (CNS) and may lead to future behavioral disorders. In various studies, offspring exposed to prenatal hypoxia showed dysfunctional changes in brain development, movement, memory and emotion ( Giannopoulou et al, 2018 ; Duran-Carabali et al, 2019 ; Zhuravin et al, 2019 ; Piesova and Mach, 2020 ). Therefore, it is crucial to study the effects of prenatal hypoxia using animal models that can replicate human embryonic development, especially fetal brain development.…”

Attentional Measures of Memory in Typically Developing and Hypoxic–Ischemic Injured Infants

“…Hypoxic-ischemic injury (HII), which occurs in 1-6/1000 live full-term births, results in increased risk for neonatal mortality and later neurodevelopmental disabilities [1,2]. The hippocampal formation, a well-known functional entity fundamental for explicit memory functions (e.g., [3][4][5]), is particularly susceptible to perinatal HII (for reviews, see [6,7]). Although many previous human studies have demonstrated atrophy of the hippocampal formation and memory impairments following HII [8][9][10][11][12][13][14][15][16], these alterations have not been noted to occur until school age [17].…”