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

Abstract

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.

Cine Phase-Contrast MR Images Failed to Predict Clinical Outcome Following ETV

“…beyond the basal cisterns and CMJ. [21][22][23] Those CSF absorption devices declined possibly due to lengthy intracranial hypertension, especially in the patient with CSF diversion. 17,20,24 In other words, the previous ETV-treated OHCP might already coexist with "communicating HCP" due to the decrease in CSF absorption even before initial ETV.…”

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET

“…Such uptake would confound the ventricular PET signal. For this reason, 11 C-PiB, which shows binding in the nasal turbinates, was not used to estimate turbinate clearance. On the other hand, 11 C-cocaine, which does not show cortical or turbinate binding, was valuable as a validator.…”

“…In rodents and other mammals, CSF is primarily cleared along olfactory nerves that traverse the cribriform plate, draining into lymphatic vessels in the nasal mucosa (7)(8)(9)(10). Rodent CSF clearance is rapid because radiolabeled albumin (11), Indian ink (7), and paramagnetic contrast (10) injected into the CSF reach the turbinates within minutes. Much less is known about human CSF clearance anatomy.…”

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

“…This system contributes to clearance of small molecules and proteins from interstitial fluid to lymph nodes in the neck and spine, and Johnston and colleagues have shown that it accounts for a large fraction of CSF clearance. [103][104][105][106] Early studies established rapid distribution of tracers inserted into interstitial fluid or CSF throughout the entire brain via perivascular fluid, and rates of tracer delivery to lymph nodes varied with head position, intracranial pressure, arterial pulsations, and other factors. 107,108 Amyloid-beta, 14 C-metabolites of [ 14 C]glucose, and fluorescent tracers are cleared via this pathway by mechanisms involving astrocytic water movements mediated by aquaporins.…”