Abstract
Background: Recent emerging evidence has highlighted the potential critical role of cerebrospinal fluid (CSF) in cerebral waste clearance and immunomodulation. It is already very well-established that the central nervous system (CNS) is completely submerged in CSF on a macro-level; but to what extent is this true on a micro-level? Specifically, within the peri-neural and peri-vascular spaces within the CNS parenchyma. Therefore, the objective of this study was to use magnetic resonance imaging (MRI) to simultaneously map the presence of CSF within all peri-neural (cranial and spinal nerves) and peri-vascular spaces in vivo in humans. Four MRI protocols each with five participants were used to image the CSF in the brain and spinal cord. Our findings indicated that all CNS neuro- and vascular-communication channels are surrounded with CSF. In other words, all peri-neural spaces surrounding the cranial and spinal nerves as well as all peri-vascular spaces surrounding MRI-visible vasculature were filled with CSF. These findings suggest that anatomically, substance exchange between the brain parenchyma and outside tissues including lymphatic ones can only occur through CSF pathways and/or vascular pathways, warranting further investigation into its implications in cerebral waste clearance and immunity.
Highlights
The critical involvement of cerebrospinal fluid (CSF) in metabolic cerebral waste clearance (CWC) has gained a lot of momentum lately
This is consistent with an array of previous studies which has already taken a closer look at the peri-neural spaces and its fluid contents, indicating that the peri-neural spaces are filled with a mixture of CSF and interstitial fluid (ISF) [24, 26,27,28,29, 42,43,44,45,46,47,48,49,50,51]
All magnetic resonance imaging (MRI)-visible vasculature were surrounded with CSF. This is the first study to simultaneously and systematically verify that all 12 pairs of cranial nerves, all MRI-visible vasculature and spinal nerves are surrounded with CSF in vivo in humans; as opposed to previous studies that have asynchronously investigated this, mainly in animals and human cadavers
Summary
The critical involvement of cerebrospinal fluid (CSF) in metabolic cerebral waste clearance (CWC) has gained a lot of momentum lately. CNS Communication Channels & CSF with the interstitial fluid, and together, they are cleared debatably though para-venous routes with any associated solutes; once again, facilitated by AQP4 [8, 13,14,15] Dysfunctions of this glymphatic pathway have been associated with a broad range of neurological diseases including, but not limited to, Alzheimer’s disease, stroke, traumatic brain injury, multiple sclerosis, diabetes, and chronic traumatic encephalopathy; begging the question of its involvement in virtually all neurodegenerative diseases [8,9,10, 12, 14, 16,17,18,19]. These findings suggest that anatomically, substance exchange between the brain parenchyma and outside tissues including lymphatic ones can only occur through CSF pathways and/or vascular pathways, warranting further investigation into its implications in cerebral waste clearance and immunity
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