Species‐specific transfer of plasma albumin from blood into different cerebrospinal fluid compartments in the fetal sheep.

Abstract

SUMMARY1. The blood-cerebrospinal fluid (CSF) transfer of endogenous sheep albumin and several exogenous species of albumin has been investigated in different CSF compartments of the immature fetal sheep brain, at an early stage of development (60 days gestation, term is 150 days) when the CSF concentration of total protein is high.2. There were marked differences in the steady-state CSF/plasma ratios for all species of albumin (including endogenous sheep albumin) between different CSF compartments. Ratios measured in the cisterna magna were significantly higher than those in the dorsal subarachnoid space, which in turn were higher than those in the lateral ventricles. The ratios for endogenous sheep albumin were (%; mean + S.E.M.): lateral ventricle (LV), 4 0 + 0 03; dorsal subarachnoid (DSA), 61 + 10; cisterna magna (CM), 13-7+08. 3. Three hours after i.v. injection, the CSF/plasma ratios for bovine albumin (LV, 2 0 + 0-2; DSA, 2 4 + 0-1; CM, 7 2 + 0-7 %) were significantly lower than the ratio for endogenous sheep albumin in all three compartments. The ratios for human albumin (LV, 0 7 + 0 2; DSA, 1P0 + 0-2; CM, 3 9 + 0-4 %) were significantly lower than those for bovine albumin.4. In all three CSF compartments, the endogenous sheep albumin ratios were higher than would be expected on the basis of transfer by passive mechanisms.Conversely, steady-state CSF/plasma ratios for [3H]sucrose and [14C]inulin were consistent with passive transfer, and there were no differences between the ratios for these markers measured in each of the three CSF regions. 7. Immunocytochemical evidence suggests that the route of transfer from blood to CSF is transcellular, through the choroid plexus epithelial cells.8. Regional variations in albumin ratios are probably due to differences in specific transfer into each CSF compartment. This is reflected in a differential immunocytochemical staining for albumin in choroid plexus epithelial cells from different regions of the brain.9. The results are discussed in terms of differences in albumin amino acid sequences, structural homologies, and transfer by a specific transcellular mechanism.

Cerebral blood flow in the anaesthetized immature sheep fetus and the response to hypercapnia

“…Pa,,J was higher in our 60 days gestation fetuses (53+ 6 mmHg) than in the other studies. High levels of J' in 60 days gestation fetal sheep have previously been reported by Dziegielewska et al (1979Dziegielewska et al ( , 1991. The high levels in the present study may have been partly due to higherPa levels in the ewes which were all positive-pressure-ventilated (see Table 1 (Table 2).…”

Embryonic cerebrospinal fluid regulates neuroepithelial survival, proliferation, and neurogenesis in chick embryos

“…On the other hand, E-CSF has a complex protein composition, and the exposure of the apical surface of neuroepithelial cells to this fluid could affect their behavior (Dziegielewska et al 1980a(Dziegielewska et al , 1980b(Dziegielewska et al , 1981(Dziegielewska et al , 1991(Dziegielewska et al , 2000Checiu et al, 1984;Gato et al, 2004). Experimental data demonstrate that the loss or modification of the composition of the E-CSF strongly decreases the neuronal cell population (Desmond and Jacobson, 1977;Desmond, 1985).…”

A developmentally regulated blood‐cerebrospinal fluid transfer mechanism for albumin in immature rats.

“…The absence of significant correlations (least squares) between paired CSF and plasma concentrations for endogenous rat albumin, and human and sheep albumin in 3-day-old rats (Table 2) would occur if a specific transfer mechanism for albumin (as previously suggested for the fetal sheep; Dziegielewska et al 1991) were saturated under normal conditions by high plasma albumin concentrations. The correlations between paired CSF and plasma concentrations for bovine albumin and the chemically modified albumins are consistent with the proposal that these molecules (also sucrose and inulin) are not recognized by a transport system and enter the CSF primarily by diffusion (which would be expected to be concentration dependent).…”

“…This greater permeability is thought to be due to unrestricted diffusion through large 'pores' that reduce in number rather than in diameter later in development (Dziegielewska, Evans, Malinowska, M0llgard, Reynolds, Reynolds & Saunders, 1979; Habgood, Knott & Saunders, 1992). In addition, most of the endogenous proteins in CSF in the immature brain are present in much higher concentrations than can be accounted for by diffusion (Dziegielewska, Evans, Lorscheider, Malinowska, M0llgard, Reynolds, Saunders, & Wilkinson, 1980a, Dziegielewska, Evans, Malinowska, M0llgard, Reynolds & Saunders, 1980bDziegielewska, Habgood, M0llgard, Stagaard & Saunders, 1991). Thus in fetal sheep CSF at 30 days gestation (term is 150 days) Dziegielewska (1982) and Dziegielewska et al (1980a, b) found that albumin (66 kDa), fetuin (48 kDa) and a-fetoprotein (64 kDa) which have very similar diffusion coefficients (albumin 6-1 cm2 s-' 10-1, fetuin 6-2 and a-fetoprotein 5 7), have very different natural steady-state CSF/plasma ratios (albumin 26%, fetuin 62 % and oc-fetoprotein 53°%).…”