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.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology*; D006860:Hydrogen Bonding / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D051379:Mice; D013668:Technetium Tc 99m Aggregated Albumin / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1
D008563:Membrane Lipids; D013668:Technetium Tc 99m Aggregated Albumin; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1