Transport of transforming growth factor-beta 2 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-beta2 (TGF-beta2) passes through the blood-brain barrier and blood-nerve barriers, after intravenous, intraperitoneal or intramuscular injections. The entry of the [125I]-TGF-beta2 to the brain was rapid, saturable and inhibited by co-injection of unlabelled TGF-beta2. In contrast, co-injection of unlabelled TGF-beta2 increased the retention of [125I]-TGF-beta2 in the blood. The [125I]-TGF-beta2 transported into the brain was localised by autoradiography to the extracellular space, and was intact as judged by SDS-PAGE. The [125I]-TGF-beta2 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-beta2 had a half-life of 4 h in the brain. These results indicate that therapeutically relevant levels of TGF-beta2 reach the brain after peripheral administration of TGF-beta2.
McLennan
Ian S
IS
Neuromuscular Research Group, Department of Anatomy and Structural Biology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand. ian.mclennan@stonebow.otago.ac.nz
Weible
Michael W
MW
Hendry
Ian A
IA
Koishi
Kyoko
K
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D021381:Protein Transport / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000378:metabolism*
D016212:Transforming Growth Factor beta