Microglia and Neonatal Brain Injury

Abstract

Microglial cells are now recognized as the "gate-keepers" of healthy brain microenvironment with their disrupted functions adversely affecting neurovascular integrity, neuronal homeostasis, and network connectivity. The perception that these cells are purely toxic under neurodegenerative conditions has been challenged by a continuously increasing understanding of their complexity, the existence of a broad array of microglial phenotypes, and their ability to rapidly change in a context-dependent manner to attenuate or exacerbate injuries of different nature. Recent studies have demonstrated that microglial cells exert crucial physiological functions during embryonic and postnatal brain development, some of these functions being unique to particular stages of development, and extending far beyond sensing dangerous signals and serving as antigen presenting cells. In this focused review we cover the roles of microglial cells in regulating embryonic vasculogenesis, neurogenesis, and establishing network connectivity during postnatal brain development. We further discuss context-dependent microglial contribution to neonatal brain injuries associated with prenatal and postnatal infection and inflammation, in relation to neurodevelopmental disorders, as well as perinatal hypoxia-ischemia and arterial focal stroke. We also emphasize microglial phenotypic diversity, notably at the ultrastructural level, and their sex-dependent influence on the pathophysiology of neurodevelopmental disorders.

Purmorphamine Attenuates Neuro-Inflammation and Synaptic Impairments After Hypoxic-Ischemic Injury in Neonatal Mice via Shh Signaling

“…In addition, immediate microglial activation occurs following HI and mediates brain injury (Hagberg et al, 2015;Shao et al, 2017). Activated microglia mainly contributes to neuro-inflammation and releases inflammatory mediators including tumor necrosis factor-α and interleukin-1β, leading to neuronal dead and excitotoxic injury (Mallard et al, 2018). Pharmacologic inhibition of microglial activation suppresses HI-induced neuronal apoptosis (Arvin et al, 2002;Li et al, 2014).…”

Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia

“…During recent years the role that microglia plays in disorders of the CNS has been thoroughly studied (Crews et al 2017;Salter and Stevens 2017). Microglia has been shown to be involved in different processes such as regulation of embryonic vasculogenesis, secretion of trophic factors, immuno-surveillance, oligodendrogenesis and neurogenesis (Mallard et al 2018). It has been observed that neuroinflamation due to hypoxia-ischemia plays a key and deleterious role in this event (Galinsky et al 2018).…”

Commentary: Brain injury in congenital heart disease—Who knows what happened first?

“…1,2 Microglial cells are known with their role in synapse formation and blood-brain barrier development in the fetal brain and their contribution to establishing network connectivity during postnatal brain development. [2][3][4] The focus on different morphologic types of microglia and their role in embryonic vasculogenesis, neurogenesis, and building neuronal network during brain development gives another glimpse of hope in bridging the knowledge gap between normoxic and hypoxic fetal brain development, particularly in the understanding of the long-term neurodevelopmental outcome in survivors with congenital heart disease. [3][4][5][6] In this issue of the Journal, Lawrence and colleagues 7 from Children's Hospital of Philadelphia report that prenatal hypoxemia alters microglial morphology in experiments that used an assembly, an ''artificial womb.''…”