All Central Nervous System Neuro- and Vascular-Communication Channels Are Surrounded With Cerebrospinal Fluid

Overview

Journal Front Neurol

Specialty Neurology

Date 2021 Jul 5

PMID 34220663

Citations 4

Authors

Lara M Fahmy

Yongsheng Chen

Stephanie Xuan

E Mark Haacke

Jiani Hu

Quan Jiang

Affiliations

Soon will be listed here.

Abstract

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 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.

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References

Zakharov A, Papaiconomou C, Johnston M . Lymphatic vessels gain access to cerebrospinal fluid through unique association with olfactory nerves. Lymphat Res Biol. 2004; 2(3):139-46. DOI: 10.1089/lrb.2004.2.139. View

Weller R, Massey A, Newman T, Hutchings M, Kuo Y, Roher A . Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. Am J Pathol. 1998; 153(3):725-33. PMC: 1853019. DOI: 10.1016/s0002-9440(10)65616-7. View

McAllister 2nd J, Chovan P . Neonatal hydrocephalus. Mechanisms and consequences. Neurosurg Clin N Am. 1998; 9(1):73-93. View

Sakka L, Coll G, Chazal J . Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis. 2011; 128(6):309-16. DOI: 10.1016/j.anorl.2011.03.002. View

Ludemann W, von Rautenfeld D, Samii M, Brinker T . Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system. Childs Nerv Syst. 2004; 21(2):96-103. DOI: 10.1007/s00381-004-1040-1. View

Arbel-Ornath M, Hudry E, Eikermann-Haerter K, Hou S, Gregory J, Zhao L . Interstitial fluid drainage is impaired in ischemic stroke and Alzheimer's disease mouse models. Acta Neuropathol. 2013; 126(3):353-64. PMC: 3810119. DOI: 10.1007/s00401-013-1145-2. View

Aoki I, Wu Y, Silva A, Lynch R, Koretsky A . In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI. Neuroimage. 2004; 22(3):1046-59. DOI: 10.1016/j.neuroimage.2004.03.031. View

McComb J . Recent research into the nature of cerebrospinal fluid formation and absorption. J Neurosurg. 1983; 59(3):369-83. DOI: 10.3171/jns.1983.59.3.0369. View

McKusick K, Strauss H, Cooney J, Taveras J . Experimental in vivo imaging of the cranial perineural lymphatic pathway. AJNR Am J Neuroradiol. 1984; 5(5):539-45. PMC: 8335123. View

10.

Carare R, Bernardes-Silva M, Newman T, Page A, Nicoll J, Perry V . Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol. 2008; 34(2):131-44. DOI: 10.1111/j.1365-2990.2007.00926.x. View

11.

Zakharov A, Papaiconomou C, Djenic J, Midha R, Johnston M . Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by subarachnoid injection of Microfil. Neuropathol Appl Neurobiol. 2003; 29(6):563-73. DOI: 10.1046/j.0305-1846.2003.00508.x. View

12.

Mollanji R, Bozanovic-Sosic R, Silver I, Li B, Kim C, Midha R . Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics. Am J Physiol Regul Integr Comp Physiol. 2001; 280(5):R1573-81. DOI: 10.1152/ajpregu.2001.280.5.R1573. View

13.

Louveau A, Herz J, Alme M, Salvador A, Dong M, Viar K . CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018; 21(10):1380-1391. PMC: 6214619. DOI: 10.1038/s41593-018-0227-9. View

14.

Albargothy N, Johnston D, MacGregor-Sharp M, Weller R, Verma A, Hawkes C . Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. Acta Neuropathol. 2018; 136(1):139-152. PMC: 6015107. DOI: 10.1007/s00401-018-1862-7. View

15.

Zakharov A, Papaiconomou C, Koh L, Djenic J, Bozanovic-Sosic R, Johnston M . Integrating the roles of extracranial lymphatics and intracranial veins in cerebrospinal fluid absorption in sheep. Microvasc Res. 2004; 67(1):96-104. DOI: 10.1016/j.mvr.2003.08.004. View

16.

Erlich S, McComb J, Hyman S, WEISS M . Ultrastructural morphology of the olfactory pathway for cerebrospinal fluid drainage in the rabbit. J Neurosurg. 1986; 64(3):466-73. DOI: 10.3171/jns.1986.64.3.0466. View

17.

Jessen N, Munk A, Lundgaard I, Nedergaard M . The Glymphatic System: A Beginner's Guide. Neurochem Res. 2015; 40(12):2583-99. PMC: 4636982. DOI: 10.1007/s11064-015-1581-6. View

18.

Bradbury M, Cserr H, Westrop R . Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit. Am J Physiol. 1981; 240(4):F329-36. DOI: 10.1152/ajprenal.1981.240.4.F329. View

19.

Boulton M, Young A, Hay J, Armstrong D, Flessner M, Schwartz M . Drainage of CSF through lymphatic pathways and arachnoid villi in sheep: measurement of 125I-albumin clearance. Neuropathol Appl Neurobiol. 1996; 22(4):325-33. DOI: 10.1111/j.1365-2990.1996.tb01111.x. View

20.

Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D . Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res. 2005; 1(1):2. PMC: 546409. DOI: 10.1186/1743-8454-1-2. View