Comparison of cerebrospinal fluid transport in fetal and adult sheep

Abstract

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 x min(-1) x cm H(2)O(-1)) or CSF outflow resistance (fetus 83.7 +/- 9.8, adult 84.7 +/- 19.7 cm H(2)O x ml(-1) x min) were observed. To confirm CSF transport to plasma in fetal animals, (125)I- or (131)I-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.

The late gestation increase in circulating ACTH and cortisol in the fetal sheep is suppressed by intracerebroventricular infusion of recombinant ovine leptin

“…In these experiments, leptin was administered intracerebroventricularly in order to achieve a significant elevation of leptin in the vicinity of the hypothalamic nuclei. Subsequently, the drainage of cerebrospinal fluid through lymphatics and arachnoid granulations allowed centrally administered leptin to enter the systemic circulation, as has been shown for other peptides (Mollanji et al 2001). Infusing recombinant ovine leptin at a rate of 20 µg/h intracerebroventricularly, we have achieved plasma levels of leptin similar to those reported in adult sheep (Blache et al 2000, Delavaud et al 2000, Ehrhardt et al 2000, Nagatani et al 2000, Morrison et al 2001, Thomas et al 2001.…”

Integration of the subarachnoid space and lymphatics: Is it time to embrace a new concept of cerebrospinal fluid absorption?

“…The rate of CSF absorption was reduced significantly by this blockage and remarkably, the data suggested that the majority (> 80%) of cranial CSF absorption occurred through the cribriform plate at opening CSF pressures in adult [59] and in newborn animals [60]. When radioactive CSF protein tracers were injected into the CSF compartment of fetal sheep, the highest concentrations were measured in lymph collected from the cervical lymphatics compared with samples obtained from the thoracic duct or plasma [61]. These data suggest that lymphatics have an important role in CSF absorption before birth as well.…”

Dilation of the olfactory bulb cavity concurrent with hydrocephalus in four small breed dogs

“…There is increasing evidence that CSF drainage takes place not only at the arachnoid villi, but also several extracranial sites [9]. The evidences for communication between the CSF pathways and the extracranial lymphatic system by the nasal lymphatics in various animals, including mice, rats, rabbits, sheep, pigs, monkeys, and humans [1,4,5,7,11] have been reported. Therefore, the nasal lymphatics might serve as a reserve mechanism for, or be primarily involved in the absorption of CSF in hydrocephalus.…”