Effect of bis (tributyl tin) oxide on permeability of the blood-brain barrier: a transient increase.

OBJECTIVES--To study the effect of bis (tributyl tin) oxide (TBTO) on permeability of the blood-brain barrier. METHODS--Electron microscopy and an x ray microanalyser with lanthanum chloride as a tracer were used, and blood tin concentrations were determined with an atomic absorption spectrophotometer. Adult male wistar rats received 0.05 ml/kg body weight of TBTO orally. RESULTS--A transient increase in paracellular permeability at the blood-brain barrier was found 2 h after the dose of TBTO. Electron dense lanthanum deposits penetrated tight junctions of the endothelia and permeated the subendothelial space. The x ray microprobe data showed an accumulation of TBTO at the tight junctions at 2 h. Leakage of tracer did not occur at 4 h, but oedematous changes in the surrounding glial cells were prominent between 4 and 8 h and had almost returned to normal by 24 h. By atomic absorption analysis, it was seen that blood tin concentrations rapidly increased at 1 h and rose to a maximum peak at 8 h, then gradually decreased to reach zero at 24 h. CONCLUSIONS--Accumulated TBTO at tight junctions could have caused the temporary replacement of calcium ion by tin, which induces a transient increase in paracellular permeability throughout the blood-brain barrier.