Albumin transfer across the choroid plexus of South American opossum (Monodelphis domestica).

Abstract

1. Blood-cerebrospinal fluid (CSF) transfer of various exogenous albumins has been investigated in developing Monodelphis domestica (South American grey short-tailed opossum) and compared with the steady-state CSF: plasma ratios for endogenous (Monodelphis) albumin. Ratios for Monodelphis albumin and human albumin were similar and were the highest at postnatal day 5 (P5) (48-2 + 4-4 and 40-6 + 4 5%, respectively). The ratio for bovine albumin was similar to the steady-state ratio for Monodelphis albumin at P7-8 but became consistently lower than the Monodelphis albumin ratio at all other ages until P32-36 when all albumins tested attained a similar low ratio. The CSF: plasma ratio of chemically modified (succinylated) bovine albumin was always significantly lower than that of other albumins, except at the oldest age examined (P32-36). 2. Immunocytochemistry showed that within the brain, albumin was confined to the lumen and endothelial cells of blood vessels. In the choroid plexus only a small proportion (0*2-1X7% of the total cell number) of epithelial cells was positive for albumin, both endogenous and exogenous, at all ages studied (except the 3rd ventricle where cells were only positive from P8). The CSF was strongly positive for all albumins. The peak proportion of positive cells and of albumin concentrations in CSF occurred at P8. These findings suggest that the primary route for penetration of albumin into CSF is directly across the choroid plexus rather than via the brain. 3. Double-labelling immunocytochemistry revealed that the same epithelial cells contained both endogenous (Monodelphis) and exogenous (human) albumin. In contrast, for succinylated albumin, at P7 only about 35% (lateral ventricle) and 50% (4th ventricle) of Monodelphis albumin-positive cells were also positive for succinylated albumin, but by P30 this proportion increased to 90 % at both sites. 4. Thus the developing choroid plexus distinguishes between different albumins. Chemical modification of albumin (succinylation) disrupts this mechanism. It is proposed that in older animals (P32-36) all of the albumin in the CSF is derived from plasma by diffusion (as in adult animals). At earlier stages of development, a proportion of the albumin in CSF also appears to be transferred from the plasma by diffusion with an additional component transferred by a mechanism that can distinguish between different species of albumin. The main route of entry of albumin to CSF seems likely to be via the choroid plexus epithelial cells.

Tissue selectivity of insulin detemir action in vivo

“…However, it is known that albumin directly penetrates into the cerebrospinal fluid across choroids plexus epithelial cells [23], and there is evidence that as lipophilicity and membrane permeability of a molecule increases, the concentration in the cerebrospinal fluid rises [24]. Moreover, one could speculate that in the presence of a low albumin concentration such as in the cerebrospinal fluid, the rate of unbound insulin detemir is increased, and therefore an enhanced amount of 'active' insulin detemir molecules is available to bind to the IR.…”

The temporospatial expression of peripheral myelin protein 22 at the developing blood‐nerve and blood‐brain barriers

“…The choroid epithelium regulates the composition of the cerebrospinal fluid (CSF), which in the mature mammalian brain has a low protein concentration compared with serum . The CSF of the immature brain contains high levels of protein that bypass restrictive tight junctions (Ek et al, 2003) and penetrate the choroid epithelium through an intracellular route (Balslev et al, 1997;Knott et al, 1997). In the embryonic mammalian brain, specialized neuroepithelial junctions are thought to enable the brain parenchyma to exclude CSF proteins (Mollgard et al, 1987), thus maintaining a restrictive environment for the immature CNS.…”

Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis Domestica)

“…The opossum was chosen because the permeability to proteins and low molecular weight markers has been extensively studied in this species during development (Knott et al, 1997;Ek et al, 2001). This gives an advantage over many previous studies as structural changes of the choroid plexus can be compared directly with the permeability of the blood-CSF barrier over a similar developmental period in the same species.…”