PERMEABILITY OF THE DEVELOPING BLOOD-BRAIN-BARRIER TO C-14 MANNITOL USING THE RAT IN-SITU BRAIN PERFUSION TECHNIQUE

The brain penetration of C-14-mannitol was investigated using a bilate ral in situ brain perfusion technique followed by capillary depletion analysis. This technique measures the uptake of slowly penetrating sol utes in the absence of the systemic circulation, and separates accumul ation in brain endothelial cells from uptake into brain parenchyma. Pe netration of C-14-mannitol was linear up to 30 min in rats aged 1, 2, 3 weeks and in adults. The brain mannitol space was higher in 1-week-o ld neonatal rats compared with adults (P < 0.05) and was due to a grea ter initial volume of distribution (V-i) for mannitol in the neonates, and not due to an elevated transfer rate (K-in). Thirty percent of ma nnitol in the neonatal brain was associated with the capillary contain ing fraction, whereas in the adult only 13% was found in this fraction . This suggests that the permeability of the blood-brain barrier to ma nnitol does not change significantly with development but that more ma nnitol is associated with endothelial cells in the neonate. An investi gation of C-14-glycine uptake was also carried out, and unlike mannito l the K-in was greater in the neonate compared to the adult suggesting an elevated rate of transfer for this amino acid into the neonatal ra t brain.