Author:
Ligocki Alexander P.,Vinson Augustine V.,Yachnis Anthony T.,Dunn William A.,Smith Douglas E.,Scott Elizabeth A.,Alvarez-Castanon Jimena V.,Montalvo Daniel E. Baez,Frisone Olivia G.,Brown Gary A.J.,Pessa Joel E.,Scott Edward W.
Abstract
AbstractCerebrospinal fluid (CSF) is an aqueous solution responsible for nutrient delivery and waste removal for the central nervous system (CNS). The three-layer meningeal coverings of the CNS support CSF flow. Peripheral nerves have an analogous three-layer covering consisting of the epineurium, perineurium, and endoneurium. Peripheral axons, located in the inner endoneurium, are bathed in “endoneurial fluid” similar to CSF but of undefined origin. CSF flow in the peripheral nervous system has not been demonstrated. Here we show CSF flow extends beyond the CNS to peripheral nerves in a contiguous flowing system. Utilizing gold nanoparticles, we identified that CSF is continuous with the endoneurial fluid and reveal the endoneurial space as the likely site of CSF flow in the periphery. Nanogold distribution along entire peripheral nerves and within their axoplasm suggests CSF plays a role in nutrient delivery and waste clearance, fundamental aspects of peripheral nerve health and disease.One Sentence SummaryCerebrospinal fluid unites the nervous system by extending beyond the central nervous system into peripheral nerves.
Publisher
Cold Spring Harbor Laboratory
Reference61 articles.
1. L. Weed , Studies on Cerebro-Spinal Fluid. No. II : The Theories of Drainage of Cerebro-Spinal Fluid with an Analysis of the Methods of Investigation. The Journal of medical research 31, (1914).
2. S. Proulx , Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics. Cellular and molecular life sciences : CMLS 78, (2021).
3. A. Louveau , B. Plog , S. Antila , K. Alitalo , M. Nedergaard , J. Kipnis , Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. The Journal of clinical investigation 127, (2017).
4. L. Sakka , G. Coll , J. Chazal , Anatomy and physiology of cerebrospinal fluid. European annals of otorhinolaryngology, head and neck diseases 128, (2011).
5. J. Iliff , M. Wang , Y. Liao , B. Plogg , W. Peng , G. Gundersen , H. Benveniste , G. Vates , R. Deane , S. Goldman , E. Nagelhus , M. Nedergaard , A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science translational medicine 4, (2012).