The brain extracellular space in chronic kidney disease

The brain extracellular space (ECS) is a highly complex structure between the innumerable and intermingled processes of brain cells (neurons and glial cells). This space represents up to 20 % of total brain volume (excluding the ventricles) and hosts an extracellular matrix of proteoglycans. The regulation of this space is unclear, though it may differ from other organs due to the presence of the blood brain barrier. Changes in the ECS may modify the diffusion timing of volume-dependent neurotransmitters such as dopamine, thus potentially altering most brain activities. Indeed, recently it has been shown that mild cognitive impairment is correlated to a reduction of ECS. Because water and electrolyte homeostasis are tightly regulated by the kidney, it is possible that a reduced kidney filtration may change the brain extracellular space and therefore explain the reduced cognitive functions exhibited during kidney diseases. The present communication explores the regulation of ECS in the presence of kidney diseases, discussing how reduced kidney function might impact on brain structure and function in both mice and humans, and suggests potential mechanisms for this link.