The impact of trophic and immunomodulatory factors on oligodendrocyte maturation: Potential treatments for encephalopathy of prematurity

Abstract

Encephalopathy of prematurity (EoP) is a major cause of morbidity in preterm neonates, causing neurodevelopmental adversities that can lead to lifelong impairments. Preterm birth‐related insults, such as cerebral oxygen fluctuations and perinatal inflammation, are believed to negatively impact brain development, leading to a range of brain abnormalities. Diffuse white matter injury is a major hallmark of EoP and characterized by widespread hypomyelination, the result of disturbances in oligodendrocyte lineage development. At present, there are no treatment options available, despite the enormous burden of EoP on patients, their families, and society. Over the years, research in the field of neonatal brain injury and other white matter pathologies has led to the identification of several promising trophic factors and cytokines that contribute to the survival and maturation of oligodendrocytes, and/or dampening neuroinflammation. In this review, we discuss the current literature on selected factors and their therapeutic potential to combat EoP, covering a wide range of in vitro, preclinical and clinical studies. Furthermore, we offer a future perspective on the translatability of these factors into clinical practice.

Modulatory effect of IL‐1 inhibition following lipopolysaccharide‐induced neuroinflammation in neonatal microglia and astrocytes

“…The addition of oligodendrocytes in in vitro co‐culture system is of interest as they are one of the main cell targets in perinatal WMI. Oligodendrocyte progenitor cells (OPC) and pre‐oligodendrocytes are highly vulnerable to pro‐inflammatory mediators and produce high levels of pro‐inflammatory modulators' receptors including for IL‐1β (Deng et al, 2014; Huang, Zhou, et al, 2020; Vaes et al, 2021). In vivo models of inflammation‐induced brain injury such as the systemic or intracerebral LPS exposure in neonatal rats allowed to evaluate the role of inflammatory mediators on oligodendrocyte lineage.…”

Altered expression of transfer RNAs and their possible roles in brain white matter injury

“…OPCs constitute a major cell fraction of the brain's white matter and are prone to HI insults [3,4]. In the present study, we explored the differential expression pattern of tRNAs in OPCs in response to HI.…”

“…Oligodendrocyte precursor cells (OPCs) are the main damaged cells in WMI [3]. The histopathological assay of WMI showed that immature oligodendrocyte differentiation was disrupted, accompanied by over-proliferation of astrocytes and microglia, leading to impaired myelin formation, which may develop into mental dysfunction and cerebral palsy in future life [4], increasing the incidence of oral diseases [5].…”

Microglia autophagy in ischemic stroke: A double-edged sword

“…In many physiological and pathological processes, microglia can produce and secrete multiple factors such as chemokines, cytokines, growth factors and inflammatory factors, and simultaneously, express a wide range of immune receptors and receptors for neurotransmitters. As an example, insulin-like growth factor-1 (IGF-1), an important pro-neurogenic factor primarily produced by microglia, can influence oligodendrogenesis instigation, stimulate neurogenesis and mediate the neuroprotective responses ( 43 – 45 ). In addition, microglia contribute majorly in the production of growth factor transforming growth factor-beta (TGF-β), which promotes cerebrovascular remodeling following a focal ischemic insult and mediates proliferation, differentiation, and maturation of neurons and glial cells in neurodegenerative diseases ( 46 , 47 ).…”