Intercellular barriers to and transcellular transfer of albumin in the fetal sheep brain

The nature of the barriers that keep proteins out of the developing brain has been studied in tissues obtained from fetal sheep in experiments conducted under controlled physiological conditions. In anaesthetised pregnant ewes, 60 day gestation fetuses (term is 150 days) were exposed to human albumin injected intravenously for periods up to 6 h. The immunocytochemical distribution of exogenous human albumin was compared with that of endogenous sheep albumin at both the light and electron-microscopical level. Immunogold labelling of ultracryosections suggests that a tubulocisternal endoplasmic reticulum system in immature choroid-plexus epithelial cells is the route by which albumin crosses from blood to cerebrospinal fluid (CSF) in the developing brain. The integrity of the blood-brain barrier, the blood-cerebrospinal fluid barrier and the cerebrospinal fluid-brain barrier to protein, was confirmed. In addition, at the outer surface of the developing brain there also appears to be a restriction on the passage of albumin from CSF into the brain. These observations support earlier proposals that the immature brain develops within an internal environment from which proteins in plasma and CSF are largely excluded.