Circulating TGF-beta1 does not cross the intact blood-brain barrier.

Transforming growth factor-beta (TGF-beta) from the periphery can cross the disrupted blood-brain barrier (BBB) to exert neuroprotective effects on the brain. Here, we quantify its permeation across the normal mouse BBB. By high-performance liquid chromatography, we show that TGF-beta1 is stable in circulating blood but does not cross the intact BBB after intravenous injection any faster than the vascular marker 99mTc-albumin. This poor rate of influx cannot be explained by rapid efflux out of the brain or lack of lipophilicity as measured by the octanol/buffer partition coefficient, although the hydrogen bonding potential was relatively high, consistent with poor penetration. Thus, the therapeutic potential of TGF-beta1 administered in blood is probably limited to situations in which the BBB has been disrupted.