Cerebral fluids and solute transport in hypertension

The main constituent of the brain is water, taking up nearly eighty percent of its weight. Most of this is present in the cells of the brain: the neurons and associated cells, i.e. astrocytes, oligodendrocytes and microglia. The extracellular fluids are blood, interstitial fluid, and cerebrospinal fluid. They supply the oxygen and other essential nutrients the cells need, and, at the same time, remove waste substances. In addition, they protect the brain from physical injury. Hence the homeostasis of these fluids is of vital importance. In this thesis, we explored the production, removal, and flow pattern of the interstitial fluid and cerebrospinal fluid, and how these processes are affected in hypertension. This revealed that hypertensive animals have a disrupted brain fluid homeostasis, possibly resulting from subtle changes at the blood-brain barrier and blood-cerebrospinal fluid barrier, accompanied by alterations in the structure and function of cerebral arteries. We furthermore demonstrated that interstitial solutes drain towards the closest cerebrospinal fluid compartment, which includes arterial perivascular spaces, and leave the brain via the cribriform plate and spinal nerves in rodents. Lastly, we described a novel post-mortem approach to study perivascular spaces in the human brain. Taken together, the work presented in this thesis further elucidates the physiology of the fluids in the brain, and provides new perspectives for future research to untangle the pathophysiological mechanisms of reduced waste clearance and the impact of hypertension on the brain.