|
 |
| REVIEW ARTICLE |
|
| Year : 2018 | Volume
: 4
| Issue : 1 | Page : 14-18 |
|
Cerebrospinal fluid circulation: What do we know and how do we know it?
Ahmad H Khasawneh1, Richard J Garling2, Carolyn A Harris1
1 Department of Neurosurgery; Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA
2 Department of Neurosurgery, Wayne State University, Detroit, MI, USA
| Date of Submission | 06-Mar-2018 |
| Date of Decision | 09-Mar-2018 |
| Date of Acceptance | 14-Mar-2018 |
| Date of Web Publication | 18-Apr-2018 |
Correspondence Address:
Dr. Carolyn A Harris
Department of Chemical Engineering and Materials Science, Secondary Appointment, Neurosurgery, Wayne State University, Detroit, MI
USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/bc.BC_3_18
The central nervous system's (CNS) complicated design is a double-edged sword. On the one hand, the complexity is what gives rise to higher order thinking; but on the other hand, damage to the CNS evokes its unforgiving nature. The cerebrospinal fluid (CSF) circulation system is an intricate system embedded in and around the CNS that has been the topic of debate since it was first described in the 18th century. It is underscored by the choroid plexus's distinct vascular network which has conventionally been seen as the most prominent structure in CSF production through a variety of active transporters and channels. Despite the ubiquity of this circulation system in vertebrates, some aspects remain understudied. Recent advances in scientific methodology and experimentation have proven to be effective tools for elucidating the mechanisms of the CSF circulation system and the pathological conditions associated with its malfunction. In this review, we capitulate the classical understanding of CSF physiology as well as a new, emerging theory on CSF production. Keywords: Absorption, circulation, CSF flow, production
How to cite this article:
Khasawneh AH, Garling RJ, Harris CA. Cerebrospinal fluid circulation: What do we know and how do we know it?. Brain Circ 2018;4:14-8 |
| Introduction | |  |
Cerebrospinal fluid (CSF) is a clear, proteinaceous fluid that exists in the surrounding spaces of mammalian central nervous systems (CNS). It is a multifaceted marvel, able to continuously support the nervous system through the lifespan of the organism. In the average adult human, there is roughly 150 mL of CSF circulating at any given moment. The ventricular portion amounts to roughly 17% of the total fluid volume, the rest of which lies in the cisterns and subarachnoid space. CSF forms at a rate of about 0.3–0.4 mL/min; translating to 18-25 mL/hour and 430–530 mL/day.[1] The classic thought is that CSF flows due to the forces generated by cardiac pulsations and pulmonary respiration. In this review, we will outline the physiology of CSF in the typical adult, as well as the pathologies associated with CSF circulation, malabsorption, and production.
The existence of CSF has been known for centuries. Hippocrates was among the first to describe the fluid as water that surrounded the brain.[2] The constant production of fluid was hypothesized, but anatomists could not describe, nor pinpoint, the means of production. It was not until Cushing published his paper “Studies on the Cerebro-Spinal Fluid” in 1914 that a source for CSF, the choroid plexus, had come to be acknowledged.[3] Dandy, soon after, conducted an experiment in which he ablated the choroid plexus of one lateral ventricle in a dog, then obstructed the foramen leading into the third ventricle; he discovered that the ventricle that was ablated and evacuated of CSF would collapse, while the ventricle that was not manipulated would expand.[4] This led to the belief that the choroid plexus is the main generator of CSF. Since then, this theory has been taken as fact, and many studies conducted on the choroid plexus and CSF secretion have revolved around this concept. The original theory of CSF production views 75% of all CSF being produced by the choroid plexus epithelium, while the remaining quarter being produced by other CNS structures such as the ependymal wall, cerebral parenchyma, and interstitial fluid (ISF).[5] Recently, however, there has been criticism regarding the design of experiments conducted by Cushing and Dandy on the choroid plexuses– calling into question the veracity of what we know about CSF.
| Cerebrospinal Fluid Production | | |
The secretion of CSF from any of the four choroid plexuses occurs as a two-stage process.[6] In the first stage, plasma is passively filtered across the fenestrated capillary endothelium into the choroidal interstitial space due to the osmotic pressure gradient between the two surfaces. The ultrafiltrate then undergoes active transport across the choroidal epithelium into the ventricular spaces.
An alternative hypothesis on the production of CSF brought about by Orešković and Klarica sheds light on new developments regarding the choroid plexus as the main site of CSF formation. They call into question nearly 100 years of research which elucidated the role of the plexuses in the CSF system, citing faulty methodologies that are highly subject to error and misinterpretation as well as experimental settings (ex vivo and in vitro) that do not represent the true physiology of the system. The authors assert that no experiment has undoubtedly confirmed the capacity of the choroid plexus to completely generate the predicted volume of CSF. The main criticism asserted is that Dandy's previously mentioned experiment was not reproducible and conducted on only a single canine subject, yet served as a foundation for the classical theory. The new working theory they posit sees CSF formation as an active process that is not affected by intracranial pressure. In balanced physiological conditions, the rate of CSF formation must be equal to the rate of absorption. They postulate that this could extend to flow rate, given that formation and absorption occur in different compartments of the system. To them, it is, therefore, logical to say that secretion of CSF is the driving force of flow and circulation if there is going to be a steady volume of CSF.[7]
Orešković and Klarica examine the implications of choroid plexectomies on CSF physiology. According to the classical theory, a choroid plexectomy should significantly reduce the overall secretion of CSF, therefore providing some pressure relief in patients who have hydrocephalus. However, this is not always the outcome of the procedure; in fact, research shows that two-thirds of patients who receive the treatment should be shunted due to the recurrence of hydrocephalus.[8] In addition, Orešković and Klarica cite a study conducted by Hammock and Millhorat on rhesus monkeys in which a choroid plexectomy was performed, yet the biochemical composition of the fluid remained normal; this suggests a lesser role for the choroid plexus in molecular transport.[9] Bearing in mind nearly a century of a century of CSF research, a critical, new theory emerged in an attempt to reconcile the apparent inconsistencies of the classical theory. The new theory takes a more systematic approach, it shifts attention to the Virchow–Robin spaces (also known as perivascular spaces), which exist between where the cerebral vasculature descends from the subarachnoid space into the CNS, perforating the pia mater.[10] It is at this junction that the formation and absorption of both interstitial and CSFs occur, driven by both hydrostatic and osmotic pressure differences between the CSF circulation system and surrounding tissue. This would indicate that CSF is continually produced throughout the circulatory route and not in localized secretory organs, and any changes in the volume of CSF are influenced by the CSF osmolarity.[9] Interestingly, however, osmolarity changes can be particularly acute, where CSF volume flow can return to normal despite hypotonic serum (sink action).[11]
While there is evidence to support these claims of CSF mixing and production, there is also a wealth of literature describing the ebbs and flows of CSF, and net flow.[12] The proposed active secretion and absorption of CSF by the entire CSF circulation system, according to Spector, ignores the mixing of CSF which is substantiated by the motile cilia present on the ependymal wall as well as the shuttling of growth factors to certain regions of the brain.[12]
| The Composition of Cerebrospinal Fluid | | |
CSF is mainly composed of water (99%), with the remaining 1% accounted for by proteins, ions, neurotransmitters, and glucose.[13] The concentration of each of these proteins, the total viscosity, and the CSF surface tension varies with pathology.[14],[15] On the apical side, epithelial cells are anchored together by tight junctions which restrict the movement of these molecules; this and intercellular gap junctions give rise to the blood–CSF barrier. The composition of CSF varies from that of serum due to the differential expression of membrane-associated channels and transport proteins, ultimately resulting in the unidirectional nature of the choroidal epithelium.[1] The apical side of the epithelium is covered in microvilli that beat with the motion of the CSF, while the basolateral side is packed with folds and creases which increase the cells' surface area, making it more suited for absorption. Compared to plasma, CSF generally contains a higher concentration of sodium, chloride, and magnesium and lower concentrations of potassium and calcium.[16] This difference is conferred by active transport from the interstitial compartment that is propagated by cytoplasmic carbonic anhydrases which produce the H + and HCO3− ions that are exchanged for Na + and Cl − by basolateral transport proteins.[1] On the apical side, active transport pumps release the ions into the ventricular spaces. Movement of water across the apical membrane has been shown to be due to the presence of aquaporin-1 (AQ-1); in fact, a study conducted by Mobasheri and Marples revealed that choroid plexus was among the tissues with the highest expression of AQ-1 in the body.[17] The method for water transport across the basolateral membrane remains to be inconclusive; many studies have seen diverging results pertaining to AQ-4, which was believed to be the prime candidate for the mechanism.
The function of CSF has been one focus of mechanistic study, and the study of disease states which influence production, absorption, or CSF composition. Other than its mechanical role, CSF plays a significant role in biochemical homeostasis throughout the CNS. It has playfully been called a “nourishing liquor,” among, others for its filtering functions.[12] New techniques to analyze proteins, lipids, hormones, and microRNAs suggest the robust diversity of CSF constituents, their diffusion, and their active transport across patient cohorts, within a patient over development or time, or dependent on a disease state.[18] Some CSF biomolecules, such as secreted growth factors, neurotransmitters, morphogens, cytokines, extracellular matrix proteins, proteins involved in permeability, binding proteins, and adhesion molecules can influence production, absorption, and periventricular tissue and CSF homeostasis. Similarly, the microenvironment composition surrounding periventricular cells, and their activity, are manipulated by changes in solute transporters and CSF pathologies.[18]
| Movement and Absorption of Cerebrospinal Fluid | | |
After production, CSF movement generally occurs through the ventricular system, assisted, in part, by ciliated ependyma which beat in synchrony.[19] CSF net flow is still generally believed to flow through the ventricular system, initiated at the lateral ventricles.[5] From the lateral ventricles, CSF flows through the left and right foramen of Monro to the third ventricle. Next, it flows through the aqueduct of Sylvius into the fourth ventricle. From the fourth ventricle, the CSF may exit through the foramen of Lushka laterally, or the foramen of Magendie medially to the subarachnoid space. Passing through the foramen of Magendie results in filling of the spinal subarachnoid space. CSF egressing through the foramen of Lushka travels into the subarachnoid space of the cisterns and subarachnoid space overlying the cerebral cortex. The CSF from the subarachnoid space is eventually reabsorbed through outpouchings into the superior sagittal sinus (SSS) known as the arachnoid granulations. Arachnoid granulations act as an avenue for CSF reabsorption into the blood circulation through a pressure-dependent gradient.[6],[20] The arachnoid granulations appear as outpouchings into the SSS due to the pressure in the subarachnoid space being greater than the venous sinus pressure (NB: direct visualization of arachnoid granulations intraoperatively would reveal the inverse).
Similar to new theories on CSF production are theories of absorption. Studies in rabbit and ovine models have revealed that CSF may also be significantly absorbed by way of cervical lymphatics.[6] CSF not reabsorbed through arachnoid granulations may reach the cervical lymphatics through two potential pathways. The first is along the subarachnoid space of exiting cranial nerves.[6],[21] This provides a direct route in which CSF may be transferred from the cisterns to the to the extracranial lymphatics. The second pathway by which CSF may reach lymphatics is along the Virchow–Robin space of arteries and veins penetrating brain parenchyma.[22] The Virchow–Robin space is the potential space surrounding penetrating arteries and veins of the brain parenchyma that may vary in size depending on pathology. When CSF is not absorbed through the classical pathway, it may enter the Virchow–Robin space or be shunted to the ISF. The ISF is a compartment with the bidirectional flow to the Virchow–Robin and subarachnoid space that is believed to be mediated by AQs; but this is the topic of ongoing research. If CSF enters the ISF, it will ultimately be reabsorbed into the bloodstream, enter the Virchow–Robin space, or reenter the subarachnoid space. From the Virchow–Robin space, CSF can reenter the subarachnoid space or be reabsorbed by cervical lymphatics dependent on the forces exerted by cardiac pulsations and pulmonary respiration.
In addition to the circulation of CSF into cervical lymphatics, there have been studies describing CSF reabsorption into the dural venous plexus. At birth, arachnoid granulations are not fully developed, and CSF absorption relies on the venous plexus of the inner surface of dura that is more robust in infants.[23],[24] Although not as extensive in adults, the dural venous plexus is still believed to play a role in absorption. Adult and fetal cadaver dissections and animal models with intradural injections have all been shown to demonstrate filling of the parasagittal dural venous plexus.[25],[26],[27] The exact mechanism of CSF uptake still has not been elucidated.[24]
| The Pathophysiology of Cerebrospinal Fluid | | |
Disruption of CSF homeostasis can result in overproduction or decreased absorption of CSF, both of which may result in pathologies; one of interest is hydrocephalus. Obstruction anywhere in the ventricular system may result in increased intracranial pressure, which can create cascades of brain abnormalities, including cell death, inflammatory cell response, and cell shedding from the ventricular wall, or manipulation of the biochemical response of the cells.[28] Common the result of obstructive hydrocephalus include tumors, intraventricular hemorrhages, and congenital webs.[29] Blockage of the ventricular system proximally at the third ventricle, aqueduct of Sylvius, or fourth ventricle prevents absorption of CSF through the classical pathway and alternative pathways such as extracranial lymphatics. Alternatively, hydrocephalus caused by decreased absorption of CSF is commonly the result of infection, meningitis, subarachnoid hemorrhage, and trauma.[29] Infection, meningitis, and subarachnoid hemorrhage lead to an inflammatory response that causes scarring and obstruction of arachnoid granulations with a resultant decrease in CSF absorption and dysregulation of CSF homeostasis. Posttraumatic hydrocephalus is a little more complex and may be multifactorial. In the event of a patient with traumatic brain injury (TBI), ventriculomegaly may result from neuronal loss, ischemic events, or increased brain compliance after a craniectomy.[30],[31] In the case of craniectomy, the dura is not closed and the bone flap may be left off for weeks to months before cranioplasty which leads to decreased resistance to CSF flow and a resultant increase in brain compliance.[20],[32] Cranioplasty may result in the resolution of these changes or the alterations in brain compliance may not be readily reversed leading to the need for ventricular shunting of the excess CSF.[31],[33] It is the increased intracranial pressure from the hydrocephalus not the ventriculomegaly that is the problem. Ex vacuo hydrocephalus, or enlarged ventricles due to loss of brain matter, is commonly seen secondary to brain atrophy. Common causes in addition to the neuronal loss seen from traumatic brain injury are any pathologies resulting in a significant neuronal loss such as dementia, alcoholism, and advanced age. In ex vacuo hydrocephalus, the ventricles are enlarged, but the brain compliance and CSF outflow resistance are not increased.
Certainly, the study of the mechanisms by which CSF circulation is produced, absorbed, and regulated is an area of ongoing research, of which can be influenced by age and pathology. Future work is needed to understand the intricacies of each.
Financial support and sponsorship
This review was supported through internal funds at Wayne State University.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Brown PD, Davies SL, Speake T, Millar ID. Molecular mechanisms of cerebrospinal fluid production. Neuroscience 2004;129:957-70.  [ PUBMED] |
| 2. | Hajdu SI. A note from history: Discovery of the cerebrospinal fluid. Ann Clin Lab Sci 2003;33:334-6. [ PUBMED] |
| 3. | Cushing H. Studies on the cerebro-spinal fluid: I. Introduction. J Med Res 1914;31:1-9. |
| 4. | Dandy WE. Experimental hydrocephalus. Ann Surg 1919;70:129-42. [ PUBMED] |
| 5. | Johanson CE, Duncan JA 3 rd, Klinge PM, Brinker T, Stopa EG, Silverberg GD, et al. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease. Cerebrospinal Fluid Res 2008;5:10. |
| 6. | Brinker T, Stopa E, Morrison J, Klinge P. A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 2014;11:10. |
| 7. | Oresković D, Klarica M. The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations. Brain Res Rev 2010a; 64:241-62. |
| 8. | Lapras C, Mertens P, Guilburd JN, Lapras C Jr., Pialat J, Patet JD, et al. Choroid plexectomy for the treatment of chronic infected hydrocephalus. Childs Nerv Syst 1988;4:139-43. |
| 9. | Oresković D, Klarica M. The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations. Brain Res Rev 2010b; 64:241-62. |
| 10. | Bulat M, Lupret V, Orehković D, Klarica M. Transventricular and transpial absorption of cerebrospinal fluid into cerebral microvessels. Coll Antropol 2008;32 Suppl 1:43-50. |
| 11. | Hochwald GM, Wald A, Malhan C. The sink action of cerebrospinal fluid volume flow. Effect on brain water content. Arch Neurol 1976;33:339-44. |
| 12. | Spector R, Robert Snodgrass S, Johanson CE. A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans. Exp Neurol 2015;273:57-68. |
| 13. | Bulat M, Klarica M. Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev 2011;65:99-112. |
| 14. | Brydon HL, Hayward R, Harkness W, Bayston R. Physical properties of cerebrospinal fluid of relevance to shunt function 2: The effect of protein upon CSF surface tension and contact angle. Br J Neurosurg 1995;9:645-51. |
| 15. | Brydon HL, Hayward R, Harkness W, Bayston R. Does the cerebrospinal fluid protein concentration increase the risk of shunt complications? Br J Neurosurg 1996;10:267-73. |
| 16. | Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis 2011;128:309-16. |
| 17. | Mobasheri A, Marples D. Expression of the AQP-1 water channel in normal human tissues: A semiquantitative study using tissue microarray technology. Am J Physiol Cell Physiol 2004;286:C529-37. |
| 18. | Johanson C, Johanson N. Merging transport data for choroid plexus with blood-brain barrier to model CNS homeostasis and disease more effectively. CNS Neurol Disord Drug Targets 2016;15:1151-80. |
| 19. | Roales-Buján R, Páez P, Guerra M, Rodríguez S, Vío K, Ho-Plagaro A, et al. Astrocytes acquire morphological and functional characteristics of ependymal cells following disruption of ependyma in hydrocephalus. Acta Neuropathol 2012;124:531-46. |
| 20. | Czosnyka Z, Czosnyka M, Lavinio A, Keong N, Pickard JD. Clinical testing of CSF circulation. Eur J Anaesthesiol Suppl 2008;42:142-5. |
| 21. | McComb JG. Recent research into the nature of cerebrospinal fluid formation and absorption. J Neurosurg 1983;59:369-83. |
| 22. | Cherian I, Beltran M, Kasper EM, Bhattarai B, Munokami S, Grasso G, et al. Exploring the virchow-robin spaces function: A unified theory of brain diseases. Surg Neurol Int 2016;7:S711-4. |
| 23. | le Gros Clark WE. On the pacchionian bodies. J Anat 1920;55:40-8. |
| 24. | Mack J, Squier W, Eastman JT. Anatomy and development of the meninges: Implications for subdural collections and CSF circulation. Pediatr Radiol 2009;39:200-10. |
| 25. | Fox RJ, Walji AH, Mielke B, Petruk KC, Aronyk KE. Anatomic details of intradural channels in the parasagittal dura: A possible pathway for flow of cerebrospinal fluid. Neurosurgery 1996;39:84-90. |
| 26. | Han H, Tao W, Zhang M. The dural entrance of cerebral bridging veins into the superior sagittal sinus: An anatomical comparison between cadavers and digital subtraction angiography. Neuroradiology 2007;49:169-75. |
| 27. | Papaiconomou C, Zakharov A, Azizi N, Djenic J, Johnston M. Reassessment of the pathways responsible for cerebrospinal fluid absorption in the neonate. Childs Nerv Syst 2004;20:29-36. |
| 28. | Guerra MM, Henzi R, Ortloff A, Lichtin N, Vío K, Jiménez AJ, et al. Cell junction pathology of neural stem cells is associated with ventricular zone disruption, hydrocephalus, and abnormal neurogenesis. J Neuropathol Exp Neurol 2015;74:653-71. |
| 29. | Vinchon M, Baroncini M, Delestret I. Adult outcome of pediatric hydrocephalus. Childs Nerv Syst 2012;28:847-54. |
| 30. | Czosnyka M, Copeman J, Czosnyka Z, McConnell R, Dickinson C, Pickard JD, et al. Post-traumatic hydrocephalus: Influence of craniectomy on the CSF circulation. J Neurol Neurosurg Psychiatry 2000;68:246-8. |
| 31. | Waziri A, Fusco D, Mayer SA, McKhann GM 2 nd, Connolly ES Jr. Postoperative hydrocephalus in patients undergoing decompressive hemicraniectomy for ischemic or hemorrhagic stroke. Neurosurgery 2007;61:489-93. |
| 32. | Shapiro K, Fried A, Takei F, Kohn I. Effect of the skull and dura on neural axis pressure-volume relationships and CSF hydrodynamics. J Neurosurg 1985;63:76-81. |
| 33. | Guyot LL, Michael DB. Post-traumatic hydrocephalus. Neurol Res 2000;22:25-8. |
| This article has been cited by | | 1 |
Acute supratentorial subdural hematoma after craniocervical junction arachnolysis in a patient with posttraumatic syringomyelia; case report and literature review |
|
| Keyvan Eghbal, Majid Reza Farrokhi, Seyed Reza Mousavi, Mohammadhadi Amir Shahpari Motlagh, Ali Kazeminezhad, Fariborz Ghaffarpasand | | Clinical Case Reports. 2023; 11(4) | | [Pubmed] | [DOI] | | | 2 |
Atransgenic mouse line for assaying tissue-specific changes in endoplasmic reticulum proteostasis |
|
| Reinis Svarcbahs, Sarah M. Blossom, Helena S. Baffoe-Bonnie, Kathleen A. Trychta, Lacey K. Greer, James Pickel, Mark J. Henderson, Brandon K. Harvey | | Transgenic Research. 2023; | | [Pubmed] | [DOI] | | | 3 |
Automatic segmentation of the choroid plexuses: method and validation in controls and patients with multiple sclerosis |
|
| Arya Yazdan Panah, Marius schmidt-Mengin, Vito Ag Ricigliano, Théodore Soulier, Bruno Stankoff, Olivier Colliot | | NeuroImage: Clinical. 2023; : 103368 | | [Pubmed] | [DOI] | | | 4 |
Biodistribution of adeno-associated virus gene therapy following CSF-directed administration |
|
| Xin Chen, Daniel A Lim, Michael W Lawlor, David Dimmock, Charles Vite, Thomas Lester, Fatemeh Tavakkoli, Chanchal Sadhu, Suyash Prasad, Steven J Gray | | Human Gene Therapy. 2023; | | [Pubmed] | [DOI] | | | 5 |
Choroid plexuses at the interface of peripheral immunity and tissue repair in multiple sclerosis |
|
| Vito A.G. Ricigliano, Bruno Stankoff | | Current Opinion in Neurology. 2023; Publish Ah | | [Pubmed] | [DOI] | | | 6 |
Elevated neurofilament light chain CSF/serum ratio indicates impaired CSF outflow in idiopathic intracranial hypertension |
|
| Sinah Engel, Johannes Halcour, Erik Ellwardt, Timo Uphaus, Falk Steffen, Frauke Zipp, Stefan Bittner, Felix Luessi | | Fluids and Barriers of the CNS. 2023; 20(1) | | [Pubmed] | [DOI] | | | 7 |
Cerebrospinal Fluid–Basic Concepts Review |
|
| Natalia Czarniak, Joanna Kaminska, Joanna Matowicka-Karna, Olga Martyna Koper-Lenkiewicz | | Biomedicines. 2023; 11(5): 1461 | | [Pubmed] | [DOI] | | | 8 |
Normal Pressure Hydrocephalus |
|
| Shaan Patel, Mekdes Ditamo, Rohan Mangal, Murdoc Gould, Latha Ganti | | Cureus. 2023; | | [Pubmed] | [DOI] | | | 9 |
DenSec: Secreted Protein Prediction in Cerebrospinal Fluid Based on DenseNet and Transformer |
|
| Lan Huang, Yanli Qu, Kai He, Yan Wang, Dan Shao | | Mathematics. 2022; 10(14): 2490 | | [Pubmed] | [DOI] | | | 10 |
Hydrocephalus in Nfix-/- Mice Is Underpinned by Changes in Ependymal Cell Physiology |
|
| Danyon Harkins, Tracey J. Harvey, Cooper Atterton, Ingrid Miller, Laura Currey, Sabrina Oishi, Maria Kasherman, Raul Ayala Davila, Lucy Harris, Kathryn Green, Hannah Piper, Robert G. Parton, Stefan Thor, Helen M. Cooper, Michael Piper | | Cells. 2022; 11(15): 2377 | | [Pubmed] | [DOI] | | | 11 |
Brain Fluid Channels for Metabolite Removal |
|
| M Maloveská, F Humeník, Z Vikartovská, N Hudáková, V Almášiová, L Krešáková, D Cížková | | Physiological Research. 2022; (2): 199 | | [Pubmed] | [DOI] | | | 12 |
Viral Induction of Novel Somatic and Germline DNA Functions in Host Arthropods Opens a New Research Frontier in Biology |
|
| Timothy W. Flegel | | Frontiers in Molecular Biosciences. 2022; 9 | | [Pubmed] | [DOI] | | | 13 |
Cerebrospinal fluid dynamics along the optic nerve |
|
| Jinqiao Sheng, Qi Li, Tingting Liu, Xiaofei Wang | | Frontiers in Neurology. 2022; 13 | | [Pubmed] | [DOI] | | | 14 |
A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases |
|
| Thea Overgaard Wichmann, Helle Hasager Damkier, Michael Pedersen | | Frontiers in Human Neuroscience. 2022; 15 | | [Pubmed] | [DOI] | | | 15 |
Perivascular spaces as a potential biomarker of Alzheimer’s disease |
|
| Miranda Lynch, William Pham, Benjamin Sinclair, Terence J. O’Brien, Meng Law, Lucy Vivash | | Frontiers in Neuroscience. 2022; 16 | | [Pubmed] | [DOI] | | | 16 |
The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans |
|
| Neel H. Mehta, Jonah Sherbansky, Angela R. Kamer, Roxana O. Carare, Tracy Butler, Henry Rusinek, Gloria C. Chiang, Yi Li, Sara Strauss, L. A. Saint-Louis, Neil D. Theise, Richard A. Suss, Kaj Blennow, Michael Kaplitt, Mony J. de Leon | | Frontiers in Physiology. 2022; 12 | | [Pubmed] | [DOI] | | | 17 |
Extracellular Vesicles from Human Cerebrospinal Fluid Are Effectively Separated by Sepharose CL-6B—Comparison of Four Gravity-Flow Size Exclusion Chromatography Methods |
|
| Vedrana Krušic Alic, Mladenka Malenica, Maša Biberic, Siniša Zrna, Lara Valencic, Aleksandar Šuput, Lada Kalagac Fabris, Karmen Wechtersbach, Nika Kojc, Mario Kurtjak, Natalia Kucic, Kristina Grabušic | | Biomedicines. 2022; 10(4): 785 | | [Pubmed] | [DOI] | | | 18 |
Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies |
|
| Kim Kramer, Neeta Pandit-Taskar, Brian H. Kushner, Pat Zanzonico, John L. Humm, Ursula Tomlinson, Maria Donzelli, Suzanne L. Wolden, Sophia Haque, Ira Dunkel, Mark M. Souweidane, Jeffrey P. Greenfield, Satish Tickoo, Jason S. Lewis, Serge K. Lyashchenko, Jorge A. Carrasquillo, Bae Chu, Christopher Horan, Steven M. Larson, Nai-Kong V. Cheung, Shakeel Modak | | Journal of Hematology & Oncology. 2022; 15(1) | | [Pubmed] | [DOI] | | | 19 |
The lymphatic vascular system: much more than just a sewer |
|
| Jörg Wilting, Jürgen Becker | | Cell & Bioscience. 2022; 12(1) | | [Pubmed] | [DOI] | | | 20 |
Intracranial emergencies in neurosurgical oncology: pathophysiology and clinical management |
|
| Christina Abi Faraj, Rita I. Snyder, Ian E. McCutcheon | | Emergency Cancer Care. 2022; 1(1) | | [Pubmed] | [DOI] | | | 21 |
Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis |
|
| Vito A.G. Ricigliano, Céline Louapre, Emilie Poirion, Annalisa Colombi, Arya Yazdan Panah, Andrea Lazzarotto, Emanuele Morena, Elodie Martin, Michel Bottlaender, Benedetta Bodini, Danielle Seilhean, Bruno Stankoff | | Neurology - Neuroimmunology Neuroinflammation. 2022; 9(6): e200026 | | [Pubmed] | [DOI] | | | 22 |
Choroid plexus perfusion and bulk cerebrospinal fluid flow across the adult lifespan |
|
| Jarrod J Eisma, Colin D McKnight, Kilian Hett, Jason Elenberger, Alexander K Song, Adam J Stark, Daniel O Claassen, Manus J Donahue | | Journal of Cerebral Blood Flow & Metabolism. 2022; : 0271678X22 | | [Pubmed] | [DOI] | | | 23 |
Long-Term Clinical Efficacy of Human Umbilical Cord Blood Mononuclear Cell Transplantation by Lateral Atlanto-Occipital Space Puncture (Gong’s Puncture) for the Treatment of Multiple System Atrophy |
|
| Dianrong Gong, Weifei Wang, Xiaoling Yuan, Haiyan Yu, Min Zhao | | Cell Transplantation. 2022; 31: 0963689722 | | [Pubmed] | [DOI] | | | 24 |
Mass spectrometry-based proteomics in neurodegenerative lysosomal storage disorders |
|
| Wenping Li, Stephanie M. Cologna | | Molecular Omics. 2022; | | [Pubmed] | [DOI] | | | 25 |
The choroid plexus and its role in the pathogenesis of neurological infections |
|
| Derick Thompson, Catherine A. Brissette, John A. Watt | | Fluids and Barriers of the CNS. 2022; 19(1) | | [Pubmed] | [DOI] | | | 26 |
Rethinking the motile cilia hypothesis of hydrocephalus |
|
| Phan Q. Duy, Ana B.W. Greenberg, William E. Butler, Kristopher T. Kahle | | Neurobiology of Disease. 2022; : 105913 | | [Pubmed] | [DOI] | | | 27 |
Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression |
|
| Noha Althubaity, Julia Schubert, Daniel Martins, Tayyabah Yousaf, Maria A. Nettis, Valeria Mondelli, Carmine Pariante, Neil A. Harrison, Edward T. Bullmore, Danai Dima, Federico E. Turkheimer, Mattia Veronese | | NeuroImage: Clinical. 2022; 33: 102926 | | [Pubmed] | [DOI] | | | 28 |
Translational Approaches for Brain Delivery of Biologics via Cerebrospinal Fluid |
|
| Shraddha S. Sadekar, Mayumi Bowen, Hao Cai, Samira Jamalian, Hanine Rafidi, Whitney Shatz-Binder, Julien Lafrance-Vanasse, Pamela Chan, William J. Meilandt, Amy Oldendorp, Alavattam Sreedhara, Ann Daugherty, Susan Crowell, Kristin R. Wildsmith, Jasvinder Atwal, Reina N. Fuji, Joshua Horvath | | Clinical Pharmacology & Therapeutics. 2022; | | [Pubmed] | [DOI] | | | 29 |
Modulation of Neuroinflammation via Selective Nanoparticle-Mediated Drug Delivery to Activated Microglia/Macrophages in Spinal Cord Injury |
|
| Cinzia Stigliano, Allison Frazier, Philip J Horner | | Advanced Therapeutics. 2022; : 2200083 | | [Pubmed] | [DOI] | | | 30 |
Hypothesis:
By-products
of vascular disruption carried in the
CSF
affect prenatal brain development
|
|
| Mark Lubinsky | | Birth Defects Research. 2022; | | [Pubmed] | [DOI] | | | 31 |
Knowledge gaps in Alzheimer's disease immune biomarker research |
|
| David G. Morgan, Michelle M. Mielke | | Alzheimer's & Dementia. 2021; | | [Pubmed] | [DOI] | | | 32 |
A beneficial role for elevated extracellular glutamate in Amyotrophic Lateral Sclerosis and cerebral ischemia |
|
| Kathryn A. Schiel | | BioEssays. 2021; : 2100127 | | [Pubmed] | [DOI] | | | 33 |
Application of contrast-enhanced magnetic resonance imaging in the assessment of blood-cerebrospinal fluid barrier integrity |
|
| Inge C.M. Verheggen,Whitney M. Freeze,Joost J.A. de Jong,Jacobus F.A. Jansen,Alida A. Postma,Martin P.J. van Boxtel,Frans R.J. Verhey,Walter H. Backes | | Neuroscience & Biobehavioral Reviews. 2021; | | [Pubmed] | [DOI] | | | 34 |
Modeling fluid–structure interactions between cerebro-spinal fluid and the spinal cord |
|
| Giulia Cardillo,Carlo Camporeale | | Journal of Fluids and Structures. 2021; 102: 103251 | | [Pubmed] | [DOI] | | | 35 |
Ventriculopleural shunt: Review of literature and novel ways to improve ventriculopleural shunt tolerance |
|
| Timothy Wong,Justin Gold,Ryan Houser,Yehuda Herschman,Raja Jani,Ira Goldstein | | Journal of the Neurological Sciences. 2021; : 117564 | | [Pubmed] | [DOI] | | | 36 |
Sulfatide in health and disease. The evaluation of sulfatide in cerebrospinal fluid as a possible biomarker for neurodegeneration |
|
| Maria Blomqvist,Henrik Zetterberg,Kaj Blennow,Jan-Eric Mĺnsson | | Molecular and Cellular Neuroscience. 2021; : 103670 | | [Pubmed] | [DOI] | | | 37 |
The regulatory roles of motile cilia in CSF circulation and hydrocephalus |
|
| Vijay Kumar,Zobia Umair,Shiv Kumar,Ravi Shankar Goutam,Soochul Park,Jaebong Kim | | Fluids and Barriers of the CNS. 2021; 18(1) | | [Pubmed] | [DOI] | | | 38 |
Discovery of Glut 1 Deficiency Syndrome: Cerebrospinal Fluid Inspiration and Serendipity |
|
| Ronald I. Jacobson | | Pediatric Neurology. 2021; | | [Pubmed] | [DOI] | | | 39 |
Factors Impacting Hydrocephalus Incidence in Intracerebral Hemorrhage: A Retrospective Analysis |
|
| Jacob Gluski,Richard J. Garling,Ari Kappel,Bushra Fathima,Robert Johnson,Carolyn A. Harris | | World Neurosurgery. 2021; | | [Pubmed] | [DOI] | | | 40 |
Biochemical evaluation of intracerebroventricular rhNAGLU-IGF2 enzyme replacement therapy in neonatal mice with Sanfilippo B syndrome |
|
| Shih-hsin Kan,Ibrahim Elsharkawi,Steven Q. Le,Heather Prill,Linley Mangini,Jonathan D. Cooper,Roger Lawrence,Mark S. Sands,Brett E. Crawford,Patricia I. Dickson | | Molecular Genetics and Metabolism. 2021; | | [Pubmed] | [DOI] | | | 41 |
Global cerebrospinal fluid as a zero-reference regularization for brain quantitative susceptibility mapping |
|
| Alexey V. Dimov,Thanh D. Nguyen,Pascal Spincemaille,Elizabeth M. Sweeney,Nicole Zinger,Ilhami Kovanlikaya,Brian H. Kopell,Susan A. Gauthier,Yi Wang | | Journal of Neuroimaging. 2021; | | [Pubmed] | [DOI] | | | 42 |
Malignant idiopathic intracranial hypertension revealed a hidden primary spinal leptomeningeal medulloblastoma |
|
| Naim Izet Kajtazi,Shahpar Nahrir,Wafa Al Shakweer,Juman Al Ghamdi,Ali Al Fakeeh,Majed Al Hameed | | BMJ Case Reports. 2021; 14(7): e243506 | | [Pubmed] | [DOI] | | | 43 |
WAVE PROPAGATION IN THE CRANIUM AND THE CEREBROSPINAL FLUID |
|
| J. C. MISRA,S. DANDAPAT,S. D. ADHIKARY | | Journal of Mechanics in Medicine and Biology. 2021; 21(01): 2050045 | | [Pubmed] | [DOI] | | | 44 |
Mutant Huntingtin Is Cleared from the Brain via Active Mechanisms in Huntington Disease |
|
| Nicholas S. Caron, Raul Banos, Christopher Yanick, Amirah E. Aly, Lauren M. Byrne, Ethan D. Smith, Yuanyun Xie, Stephen E.P. Smith, Nalini Potluri, Hailey Findlay Black, Lorenzo Casal, Seunghyun Ko, Daphne Cheung, Hyeongju Kim, Ihn Sik Seong, Edward J. Wild, Ji-Joon Song, Michael R. Hayden, Amber L. Southwell | | The Journal of Neuroscience. 2021; 41(4): 780 | | [Pubmed] | [DOI] | | | 45 |
Lumbar Puncture: Indications, Challenges and Recent Advances |
|
| Biswamohan Mishra,Venugopalan Y Vishnu | | Neurology. 2021; 17(1): 23 | | [Pubmed] | [DOI] | | | 46 |
Effect of Cerebrospinal Fluid on Fibroblasts Concerning Epidural Fibrosis: An In Vitro Study |
|
| Doga Gürkanlar,Sevda Lafci Fahrioglu,Umut Fahrioglu | | The EuroBiotech Journal. 2021; 5(3): 100 | | [Pubmed] | [DOI] | | | 47 |
Waste Clearance in the Brain |
|
| Jasleen Kaur,Lara M. Fahmy,Esmaeil Davoodi-Bojd,Li Zhang,Guangliang Ding,Jiani Hu,Zhenggang Zhang,Michael Chopp,Quan Jiang | | Frontiers in Neuroanatomy. 2021; 15 | | [Pubmed] | [DOI] | | | 48 |
Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation |
|
| Anita Horvatic, Andrea Gelemanovic, Boris Pirkic, Ozren Smolec, Blanka Beer Ljubic, Ivana Rubic, Peter David Eckersall, Vladimir Mrljak, Mark McLaughlin, Marko Samardžija, Marija Lipar | | International Journal of Molecular Sciences. 2021; 22(21): 11678 | | [Pubmed] | [DOI] | | | 49 |
Computational identification and characterization of glioma candidate biomarkers through multi-omics integrative profiling |
|
| Lin Liu,Guangyu Wang,Liguo Wang,Chunlei Yu,Mengwei Li,Shuhui Song,Lili Hao,Lina Ma,Zhang Zhang | | Biology Direct. 2020; 15(1) | | [Pubmed] | [DOI] | | | 50 |
Mechanism of Coup and Contrecoup Injuries Induced by a Knock-Out Punch |
|
| Milan Toma,Rosalyn Chan-Akeley,Christopher Lipari,Sheng-Han Kuo | | Mathematical and Computational Applications. 2020; 25(2): 22 | | [Pubmed] | [DOI] | | | 51 |
The Cranial Bowl in the New Millennium and Sutherlandćs Legacy for Osteopathic Medicine: Part 1 |
|
| Bruno Bordoni,Stevan Walkowski,Bruno Ducoux,Filippo Tobbi | | Cureus. 2020; | | [Pubmed] | [DOI] | | | 52 |
Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus |
|
| Zhangyang Wang,Yiying Zhang,Fan Hu,Jing Ding,Xin Wang | | CNS Neuroscience & Therapeutics. 2020; | | [Pubmed] | [DOI] | | | 53 |
Cerebrospinal fluid: Profiling and fragmentation of gangliosides by ion mobility mass spectrometry |
|
| Mirela Sarbu,Shannon Raab,Lucas Henderson,Dragana Fabris,Željka Vukelic,David E. Clemmer,Alina D. Zamfir | | Biochimie. 2020; 170: 36 | | [Pubmed] | [DOI] | | | 54 |
Brain Ventricular System and Cerebrospinal Fluid Development and Function: Light at the End of the Tube |
|
| Ryann M. Fame,Christian Cortés-Campos,Hazel L. Sive | | BioEssays. 2020; 42(3): 1900186 | | [Pubmed] | [DOI] | | | 55 |
Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review |
|
| Marlčne Rasschaert,Roy O. Weller,Josef A. Schroeder,Christoph Brochhausen,Jean-Marc Idée | | Journal of Magnetic Resonance Imaging. 2020; | | [Pubmed] | [DOI] | | | 56 |
A comprehensive review of therapeutic targets that induce microglia/macrophage-mediated hematoma resolution after germinal matrix hemorrhage |
|
| Jerry J. Flores,Damon Klebe,Jiping Tang,John H. Zhang | | Journal of Neuroscience Research. 2019; | | [Pubmed] | [DOI] | | | 57 |
The year in review: progress in brain barriers and brain fluid research in 2018 |
|
| Richard F. Keep,Hazel C. Jones,Lester R. Drewes | | Fluids and Barriers of the CNS. 2019; 16(1) | | [Pubmed] | [DOI] | | | 58 |
Benign Postnatal Outcome after Prenatal Diagnosis of Fetal Ventriculomegaly with Choroid Plexus Hyperplasia: A Case Report |
|
| Dalila Forte, Mariana Cardoso Diogo, Carla Conceiçăo, Amets Sagarribay | | Pediatric Neurosurgery. 2019; 54(4): 258 | | [Pubmed] | [DOI] | | | 59 |
The Glymphatic and Meningeal Lymphatic System |
|
| Vinita Balasubramanya | | Materials and Methods. 2019; 9 | | [Pubmed] | [DOI] | | | 60 |
Inflammation is correlated with severity and outcome of cerebral venous thrombosis |
|
| Liyan Wang,Jiangang Duan,Tingting Bian,Ran Meng,Longfei Wu,Zhen Zhang,Xuxiang Zhang,Chunxiu Wang,Xunming Ji | | Journal of Neuroinflammation. 2018; 15(1) | | [Pubmed] | [DOI] | |
|
 |
|
|
|
Search Pubmed for