Neurofluids: A holistic approach to their physiology, interactive dynamics and clinical implications for neurological diseases

Abstract

There is increasing interest in understanding the physiology of the extracellular fluid compartments in the central nervous system and their dynamic interaction. Such interest has been in part prompted by a vigorous resurgence of the role of the venous system, the recent discoveries of the meningeal lymphatics, the brain waste removal mechanisms and their potential link to neurological diseases, such as idiopathic intracranial hypertension, Ménière’s disease, migraine, small vessel disease, and most neurodegenerative diseases. The rigid cranial cavity houses several space-competing material compartments: the brain parenchyma (BP) and four extracellular fluids, namely arterial, venous, cerebrospinal fluid (CSF) and interstitial fluid (ISF). During cardiac pulsations, the harmonious, temporal and spatial dynamic interaction of all these fluid compartments and the BP assures a constant intracranial volume at all times, consistent with the Monro-Kellie hypothesis. The dynamic interaction involves high-pressure input of arterial blood during systole and efflux of CSF into the spinal subarachnoid space (SSAS) followed by venous blood exiting directly into the vertebral and internal jugular veins towards the heart and intraventricular CSF displacing caudally towards the SSAS. Arterial pulsatile energy is transmitted to the BP that contributes to the smooth movement of fluids in and out of the brain. Perturbing any of these fluid compartments will alter the entire brain dynamics, potentially increase intracranial pressure, affect perfusion and hamper clearance capacity of metabolic waste. This review of all major extracellular fluid compartments within the brain, advocates a holistic approach to our understanding of the fluid dynamics, rather than focusing on a single compartment when analyzing neurological diseases. This approach may contribute to advance our comprehension of some common neurological disorders, paving the way to newer treatment options.

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

“…Perturbing any of these fluid compartments can alter the brain dynamics, potentially increasing intracranial pressure, affecting perfusion, and hampering the clearance of metabolic waste. [34][35][36]…”

Cerebral Vessels: An Overview of Anatomy, Physiology, and Role in the Drainage of Fluids and Solutes

“…Damage to cerebral vasculature and reduction in cerebral perfusion initiate a cascade of events that rapidly leads to disturbed cellular homeostasis and death of neurons and glial cells ( 1 ). The cerebral arterial network of vessels is unique in its anatomy, and its flow dynamics is inextricably intertwined with those of other fluids such as venous blood, cerebrospinal fluid (CSF), and the interstitial fluid (ISF) ( 2 , 3 ). Emerging evidence regarding the role of cerebral vasculature in the drainage of solutes and fluids adds to the complexity of the overall interaction with neurofluids.…”

“…The walls of dural venous sinuses are also home to meningeal lymphatic vessels ( 7 , 8 ), with a role in the drainage of CSF. In this review, a brief overview of the current evidence for the anatomy and function of vessels in the brain will be provided, followed by a summary of mechanisms of interaction of what we term “neurofluids”: blood, CSF, and ISF ( 2 ). A disruption of such mechanisms will trigger a series of pathological events such as microvascular injury, failure of ISF drainage, local deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), focal ischemia, and demyelination.…”

Imaging for central nervous system (CNS) interstitial fluidopathy: disorders with impaired interstitial fluid dynamics

“…In order to describe the fluid within the brain including the interstitial space, the term “neurofluids” was used by Toro et al as the project title of a series of studies simulating the entire fluid dynamics of the central nervous system (CNS) with a mathematical model. “Neurofluids” is defined as a collective term for the fluids in which the CNS is immersed, including the blood, CSF, and ISF [ 2 , 3 ]. This term can be helpful for understanding the ISF/CSF dynamics.…”