Cerebrospinal fluid outflow resistance in sheep: impact of blocking cerebrospinal fluid transport through the cribriform plate

We quantified cerebrospinal fluid (CSF) transport (conductance) and CSF outflow resistance in late-gestation fetal and adult sheep using two methods, a constant pressure infusion method and a bolus injection technique into the lateral ventricles. No significant differences in CSF conductance (fetus 0.013 ± 0.002, adult 0.014 ± 0.003 ml · min−1 · cmH2O−1) or CSF outflow resistance (fetus 83.7 ± 9.8, adult 84.7 ± 19.7 cmH2O · ml−1 · min) were observed. To confirm CSF transport to plasma in fetal animals,125I- or 131I-labeled human serum albumin (HSA) was injected into the lateral ventricles. The tracer entered fetal plasma with an average mass transport rate of 1.91 ± 0.47% injected/h ( n = 9). In two fetuses, we monitored the tracer appearance in plasma and cervical and thoracic duct lymph after injection of radioactive HSA into the ventricular CSF. As was the case in adult animals, fetal tracer concentrations increased in all three compartments over time, with the highest concentrations measured in lymph collected from the cervical lymphatics. These results 1) indicate that global CSF transport parameters in the late-gestation fetus and adult sheep are similar and 2) suggest an important role for extracranial lymphatic vessels in CSF transport before birth.

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Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

10.1101/485995 ◽

2018 ◽

Author(s):

Jordan N. Norwood ◽

Qingguang Zhang ◽

David Card ◽

Amanda Craine ◽

Timothy M. Ryan ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Transport ◽

Neurological Diseases ◽

Physiological Role ◽

Cribriform Plate ◽

Sensory Nerves ◽

Anatomical Basis ◽

Outflow Pathway ◽

The Brain

AbstractCerebrospinal fluid (CSF) flows through the brain, transporting chemical signals and removing waste. CSF production in the brain is balanced by a constant outflow of CSF, the anatomical basis of which is poorly understood. Here we characterized the anatomy and physiological function of the CSF outflow pathway along the olfactory sensory nerves through the cribriform plate, and into the nasal epithelia. Chemical ablation of olfactory sensory nerves greatly reduced outflow of CSF through the cribriform plate. The reduction in CSF outflow did not cause an increase in intracranial pressure (ICP), consistent with an alteration in the pattern of CSF drainage or production. Our results suggest that damage to olfactory sensory neurons (such as from air pollution) could contribute to altered CSF turnover and flow, providing a potential mechanism for neurological diseases.

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Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00235.2006 ◽

2006 ◽

Vol 291 (5) ◽

pp. R1383-R1389 ◽

Cited By ~ 48

Author(s):

Gurjit Nagra ◽

Lena Koh ◽

Andrei Zakharov ◽

Dianna Armstrong ◽

Miles Johnston

Keyword(s):

Skeletal Muscle ◽

Cerebrospinal Fluid ◽

Fluid Transport ◽

Quantitative Measure ◽

Average Concentration ◽

Cribriform Plate ◽

Major Pathway ◽

Tissue Samples ◽

Tissue Sections ◽

Novel Concept

A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport,125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20, 30, 40, and 60 min after injection, and tissue samples, including blood (from heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised for radioactive assessment. The remains were frozen. To sample the olfactory turbinates, angled coronal tissue sections anterior to the cribriform plate were prepared from the frozen heads. The average concentration of125I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 min after injection. At this point, the recoveries of injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates, 1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and 0.09% tail. The current belief that arachnoid projections are responsible for CSF drainage fails to explain some important issues related to the pathogenesis of CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates further supports a role for lymphatics in CSF absorption and provides the basis of a method to investigate the novel concept that diseases associated with the CSF system may involve impaired lymphatic CSF transport.

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Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00173.2002 ◽

2002 ◽

Vol 283 (4) ◽

pp. R869-R876 ◽

Cited By ~ 42

Author(s):

C. Papaiconomou ◽

R. Bozanovic-Sosic ◽

A. Zakharov ◽

M. Johnston

Keyword(s):

Cerebrospinal Fluid ◽

Constant Pressure ◽

Cribriform Plate ◽

Outflow Resistance ◽

Arachnoid Villi ◽

Relative Paucity ◽

Stage Of Development ◽

Cerebrospinal Fluid Absorption ◽

Essential Function ◽

Lymphatic Pathways

Arachnoid villi and granulations are thought to represent the primary sites where cerebrospinal fluid (CSF) is absorbed. However, these structures do not appear to exist in the fetus but begin to develop around the time of birth and increase in number with age. With the use of a constant pressure-perfusion system in 2- to 6-day-old lambs, we observed that global CSF transport (0.012 ± 0.003 ml · min−1 · cmH2O−1) and CSF outflow resistance (96.5 ± 17.8 cmH2O · ml−1 · min) were very similar to comparable measures in adult animals despite the relative paucity of arachnoid villi at this stage of development. In the neonate, the recovery patterns of a radioactive protein CSF tracer in various lymph nodes and tissues indicated that CSF transport occurred through multiple lymphatic pathways. An especially important route was transport through the cribriform plate into extracranial lymphatics located in the nasal submucosa. To investigate the importance of the cribriform route in cranial CSF clearance, the cranial CSF compartment was isolated surgically from its spinal counterpart. When the cribriform plate was sealed extracranially under these conditions, CSF transport was impaired significantly. These data demonstrate an essential function for lymphatics in neonatal CSF transport and imply that arachnoid projections may play a limited role earlier in development.

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Decision letter: Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

10.7554/elife.44278.024 ◽

2019 ◽

Author(s):

Roxana Carare ◽

Robert G Thorne ◽

Jeff Illif

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Transport ◽

Physiological Role ◽

Cribriform Plate ◽

Anatomical Basis

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Author response: Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

10.7554/elife.44278.025 ◽

2019 ◽

Author(s):

Jordan N Norwood ◽

Qingguang Zhang ◽

David Card ◽

Amanda Craine ◽

Timothy M Ryan ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Transport ◽

Physiological Role ◽

Cribriform Plate ◽

Author Response ◽

Anatomical Basis

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Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

eLife ◽

10.7554/elife.44278 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 18

Author(s):

Jordan N Norwood ◽

Qingguang Zhang ◽

David Card ◽

Amanda Craine ◽

Timothy M Ryan ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fluid Transport ◽

Neurological Diseases ◽

Physiological Role ◽

Cribriform Plate ◽

Sensory Nerves ◽

Anatomical Basis ◽

Outflow Pathway ◽

The Brain

Cerebrospinal fluid (CSF) flows through the brain, transporting chemical signals and removing waste. CSF production in the brain is balanced by a constant outflow of CSF, the anatomical basis of which is poorly understood. Here, we characterized the anatomy and physiological function of the CSF outflow pathway along the olfactory sensory nerves through the cribriform plate, and into the nasal epithelia. Chemical ablation of olfactory sensory nerves greatly reduced outflow of CSF through the cribriform plate. The reduction in CSF outflow did not cause an increase in intracranial pressure (ICP), consistent with an alteration in the pattern of CSF drainage or production. Our results suggest that damage to olfactory sensory neurons (such as from air pollution) could contribute to altered CSF turnover and flow, providing a potential mechanism for neurological diseases.

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Differentiated approach to plastic surgery of cerebrospinal fluid fistulas in the cribriform plate on the analysis of computed tomograms.

Folia Otorhinolaryngologiae et Pathologiae Respiratoriae ◽

10.33848/foliorl23103825-2021-27-3-22-35 ◽

2021 ◽

Vol 27 (3) ◽

pp. 22-35

Author(s):

E.V. Shelesko ◽

N.A. Chernikova ◽

Y.V. Strunina ◽

S.D. Nikonova ◽

A.H. Abdulgamidov ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Plastic Surgery ◽

Cribriform Plate

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Iatrogenic cerebrospinal fluid leak after repeated nasal swab tests for COVID-19: illustrative case

Journal of Neurosurgery: Case Lessons ◽

10.3171/case21421 ◽

2021 ◽

Vol 2 (17) ◽

Author(s):

Johnson Ku ◽

Chieh-Yi Chen ◽

Jason Ku ◽

Hsuan-Kan Chang ◽

Jau-Ching Wu ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Nasal Cavity ◽

Nasal Swab ◽

Cerebrospinal Fluid Leak ◽

Cribriform Plate ◽

Csf Leak ◽

Illustrative Case ◽

Endoscopic Endonasal ◽

Csf Rhinorrhea ◽

Csf Leakage

BACKGROUND Nasal swab tests are one of the most essential tools for screening coronavirus disease 2019 (COVID-19). The authors report a rare case of iatrogenic cerebrospinal fluid (CSF) leak from the anterior skull base after repeated nasal swab tests for COVID-19, which was treated with endoscopic endonasal repair. OBSERVATIONS A 41-year-old man presented with clear continuous rhinorrhea through his left nostril for 5 days after repeated nasal swabbing for COVID-19. There were no obvious risk factors for spontaneous CSF leak. Computed tomography cisternography showed contrast accumulation in the left olfactory fossa and along the left nasal cavity. Such findings aligned with a preliminary diagnosis of CSF leakage through the left cribriform plate. Magnetic resonance imaging confirmed the presence of a CSF fistula between his left cribriform plate and superior nasal concha. The patient underwent endoscopic endonasal repair. CSF rhinorrhea ceased after the surgery, and no recurrence was noted during the 12-week postoperative follow-up period. LESSONS Although rare, iatrogenic CSF leakage can be a serious complication following COVID-19 nasal swab tests, especially when infection may cause significant neurological sequelae. Healthcare providers should become familiar with nasal cavity anatomy and be well trained in performing nasal swab tests.

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