Title:Cholesterol in Brain Development and Perinatal Brain Injury: More than
a Building Block
Volume: 20
Issue: 7
Author(s): Fuxin Lu, Donna M. Ferriero and Xiangning Jiang*
Affiliation:
- Departments of Neurology, University of California San Francisco, San Francisco, CA, USA
Keywords:
Cholesterol, brain development, brain injury, CNS, encephalopathy, neuroplasticity.
Abstract: The central nervous system (CNS) is enriched with important classes of lipids, in which
cholesterol is known to make up a major portion of myelin sheaths, besides being a structural and
functional unit of CNS cell membranes. Unlike in the adult brain, where the cholesterol pool is relatively
stable, cholesterol is synthesized and accumulated at the highest rate in the developing brain
to meet the needs of rapid brain growth at this stage, which is also a critical period for neuroplasticity.
In addition to its biophysical role in membrane organization, cholesterol is crucial for brain development
due to its involvement in brain patterning, myelination, neuronal differentiation, and synaptogenesis.
Thus any injuries to the immature brain that affect cholesterol homeostasis may have
long-term adverse neurological consequences. In this review, we describe the unique features of
brain cholesterol biosynthesis and metabolism, cholesterol trafficking between different cell types,
and highlight cholesterol-dependent biological processes during brain maturation. We also discuss
the association of impaired cholesterol homeostasis with several forms of perinatal brain disorders
in term and preterm newborns, including hypoxic-ischemic encephalopathy. Strategies targeting the
cholesterol pathways may open new avenues for the diagnosis and treatment of developmental brain
injury.