Plasma cholesterol levels and brain development in preterm newborns

Abstract

Objective:To assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostrucural regional brain development in preterm newborns.Methods:Sixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, 3rd edition.Results:Early plasma lathosterol levels were associated with increased axial and radial diffusivity, and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.Conclusions:Higher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter which may signify regional edema, and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes.

Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats

“…Besides, we can not exclude that systemic effect of atorvastatin on cholesterol synthesis may be influencing the atorvastatin-induced effects. One previous study has revealed that higher cholesterol is associated with impaired white matter development and worse motor outcomes in preterm newborns [ 67 ]. Puglielli et al [ 68 ] have found that increased cholesterol can lead to the development of Alzheimer’s disease.…”

Cholesterol in Brain Development and Perinatal Brain Injury: More than a Building Block

“…Lanosterol, the first sterol committed to cholesterol synthesis and, therefore, considered as a surrogate for cholesterol, is able to induce mild depolarization of mitochondria and promote autophagy and protect dopaminergic neurons from cell death in a model of Parkinson’s disease [ 17 ]. Higher plasma lathosterol, another marker of endogenous cholesterol synthesis, is associated with impaired white matter development and worse motor outcomes in preterm newborns [ 18 ]. Further upstream in the isoprenoid pathway, geranylgeraniol (GG) formed from farnesyl pyrophosphate (FPP) and geranylgeranyl-PP is found to be required for hippocampal long-term potentiation (LTP) and learning/memory [ 19 ].…”

“…In addition, a clinical study assessing the relationship between plasma cholesterol levels and brain development in 60 preterm infants showed that higher early endogenous cholesterol synthesis represented by higher lathosterol levels is associated with subcortical white matter edema and worse motor outcomes. Higher early blood cholesterol is associated with improved cerebellar volumes [ 18 ]. Although plasma cholesterol is separate from brain cholesterol, the issues in nutrition/metabolism, infections/immune system, the liver, or cardiovascular system that affect blood cholesterol may indirectly impact brain development in premature babies.…”

Oligodendrocyte Development and Implication in Perinatal White Matter Injury

“…In this regard, short- and long-chain polyunsaturated fatty acids (PUFAs) as well as cholesterol are indispensable building blocks for myelin production ( Dimas et al, 2019 ; Hussain et al, 2019 ). Disturbance of cholesterol homeostasis following HI in neonatal brain was associated with worse subcortical white matter development ( Kamino et al, 2019 ; Marangon et al, 2020 ). To this end, an ongoing clinical trial is currently evaluating the effect of early nutritional supply in brain maturation and neonatal outcomes in preterm infants ( ClinicalTrials.gov NCT03555019) ( Chan et al, 2016 ; Wendel et al, 2021 ).…”