The Potential Roles of Blood-Brain Barrier and Blood-Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a privileged organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood-brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood-CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.

Automated summary

Manganese is an essential trace nutrient for life, but can become neurotoxic at high concentrations in the brain. The brain consists of two barriers - the blood-brain barrier (BBB) formed by endothelial cells and the blood-CSF barrier (BCB) formed by the choroid plexus - that prevent substances in the systemic circulation from reaching the brain and spinal cord. Studies have provided insights into manganese transport and metabolism in the brain, with a focus on the roles of the BBB and BCB in maintaining brain manganese homeostasis.