The thyroid hormones (THs) are synthesized outside the brain and have important effects on the growth, development and metabolism of the central nervous system (Moore et al. 1973; Pickard et al. 1987).The entry of thyroxine (T4) into the brain is via two main barriers, the blood-brain and the blood- cerebrospinal fluid (CSF) barriers, the choroid plexus (CP). However, the transport route of T4 from the CSF compartments is still not fully understood. The aim of this research was to characterise the mechanism by which T4 is transported from the CSF across the lateral CP. Therefore we investigated the effect of sodium replacement with choline in ACSF on 125I-labelled T4 transport at the apical side of the CP using the steady-state method with 125I-T4 in the ACSF to calculate CSF to blood movement (R %) in the in situ perfused CP of the sheep. Sheep were anaesthetised with 20 mg kg-1 thiopentone (I.V.), heparinised and exsanguinated, and killed humanely. The brain was removed and the CP perfused with a modified Ringer solution via the internal carotid arteries. Both ventricles were then opened and the CP was superfused with ACSF containing 0.5 mCi 125I-labelled T4 and 10 mCi 14C-labelled mannitol per 100 ml of ACSF. The steady-state uptake of 125I-labelled T4 was achieved after 1 h perfusion, then the ACSF was replaced with a low Na+ ACSF. The results have shown that the control value for the 125I-labelled T4 after 1 h across CP was 0.012 ± 0.0013 (n = 9) and in the presence of low Na+ was 0.006 ± 0.0005 (n = 3) (means ± S.E.M., P < 0.05, Student’s unpaired t test).
These preliminary findings indicate that the significant reduction in the transport of T4 from the CSF to the blood across the CP epithelial cells might be largely due to a Na+-dependent mechanism present on the apical side of the CP cells, an important factor in T4 transport into the CNS. Work is in progress to determine the mechanism of this effect.
This work was funded by Al-Tajir World of Islam Trust.
All procedures accord with current UK legislation.