Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease

Abstract

Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer’s disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the ‘glymphatic’ system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions.

Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature

“…Although most cell types elaborate short primary cilia, longer motile cilia are present on the surface of specialized cells and function to generate directional extracellular fluid flow in several contexts. Cilia-directed flow within early embryonic organizers breaks left-right (L-R) symmetry (14) and CSF flow, which is critical for central nervous system homeostasis (15), is generated by the polarized beating of EC cilia lining brain ventricles (16). Notably, abnormal L-R asymmetries and defective CSF flow have been observed in IS patients (17) and an elevated incidence of scoliosis has been documented among primary ciliary dyskinesia (PCD) patients (18).…”

Tissue mechanics regulate brain development, homeostasis and disease

“…The inability of cells to return to homeostasis can result in problems, such as dementia and neurodegeneration that can manifest several years later (Smith et al, 2013). Brain degeneration is associated with problems in protein folding and clearance (Hetz and Mollereau, 2014), and recent findings also demonstrate a correlation between ECM composition and/or mechanical changes, altered CSF dynamics and the onset of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's Disease (Bonneh-Barkay and Wiley, 2009;Tyler, 2012;Simon and Iliff, 2016).…”

Cervical pseudomeningocele-induced hydrocephalus following traumatic brachial plexus injury-–a case report

“…Often cited as "the third circulation [9], CSF is a heterogeneous fluid composed of plasma filtration and cell segregation products [10]. The choroid plexus and surrounding structures [3] produces CSF, which flows into the ventricles and eventually drains into arachnoid granulations and the main venous system of the brain [11,12]. The described processes maintain CSF homeostasis between production and absorption.…”