Abstract
The glymphatic system is a newly discovered waste drainage pathway in the brain; it plays an important role in many neurological diseases. Ongoing research utilizing various cerebrospinal fluid tracer infusions, either directly or indirectly into the brain parenchyma, is investigating clearance pathways by using distinct imaging techniques. In the present review, we discuss the role of the glymphatic system in various neurological diseases and efflux pathways of brain waste clearance based on current evidence and controversies. We mainly focus on new magnetic resonance imaging (MRI) modeling techniques, along with traditional computational modeling, for a better understanding of the glymphatic system function. Future sophisticated modeling techniques hold the potential to generate quantitative maps for glymphatic system parameters that could contribute to the diagnosis, monitoring, and prognosis of neurological diseases. The non-invasive nature of MRI may provide a safe and effective way to translate glymphatic system measurements from bench-to-bedside.
Highlights
According to the traditional understanding of cerebrospinal fluid (CSF) dynamics, CSF passes from the lateral ventricles to the third ventricle through the interventricular foramen of Monro and goes to the fourth ventricle through the cerebral aqueduct of Sylvius [1,2]
Another magnetic resonance imaging (MRI) study in non-human primates showed significant CSF circulation impairment in the brain parenchyma after subarachnoid hemorrhage (SAH), which may lead to the dysfunction of the glymphatic system [43]
We have demonstrated a reduction in tracer clearance in rat models of diabetesmellitus mellitus (DM) compared to age matched controls using MRI [36]
Summary
According to the traditional understanding of cerebrospinal fluid (CSF) dynamics, CSF (which is mainly produced by the choroid plexus at a rate of 0.3–0.4 mL/min) passes from the lateral ventricles to the third ventricle through the interventricular foramen of Monro and goes to the fourth ventricle through the cerebral aqueduct of Sylvius [1,2]. The resulting CSF-ISF fluid exchange and the interstitial waste solutes exit along explicit peri-venous spaces alongside parenchymal venous blood vessels [5,6,13,14], as demonstrated in Figure 1 [15]. Cardiac systole, are thought to be the major contributor to the CSF bulk flow and CSF-ISF fluid exchange through AQP-4, providing solute transport from peri-arterial spaces into the extracellular brain tissue [14,19,20]. ISF and interstitial waste in the parenchyma with the of AQP-4 and White gaps between end-feet, and exit via solutes perivenous efflux pathway (along thehelp perivenous space). Reproduced with permission from [15]
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