Transport of transforming growth factor-β2 across the blood-brain barrier

The blood-brain barrier acts as an interface between the brain and body through a combination of restrictive mechanisms and transport processes. Substances essential for brain function pass through the barrier either by passive diffusion or by active transport. We report here that [125I]-transforming growth factor-β2 (TGF-β2) passes through the blood-brain barrier and blood-nerve barriers, after intravenous, intraperitoneal or intramuscular injections. The entry of the [125I]-TGF-β2 to the brain was rapid, saturable and inhibited by co-injection of unlabelled TGF-β2. In contrast, co-injection of unlabelled TGF-β2 increased the retention of [125I]-TGF-β2 in the blood. The [125I]-TGF-β2 transported into the brain was localised by autoradiography to the extracellular space, and was intact as judged by SDS-PAGE. The [125I]-TGF-β2 was widely distributed throughout the brain, with the highest concentrations in the hypothalamus and nerves and the lowest in the cerebral hemispheres. The [125I]-TGF-β2 had a half-life of 4 h in the brain. These results indicate that therapeutically relevant levels of TGF-β2 reach the brain after peripheral administration of TGF-β2.