Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biological Transport / drug effects
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Blood-Brain Barrier / drug effects*
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Blood-Brain Barrier / physiology*
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Hydrogen Bonding / drug effects
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Injections, Intravenous
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Male
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Membrane Lipids / chemistry
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Metabolic Clearance Rate / drug effects
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Metabolic Clearance Rate / physiology
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Mice
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Technetium Tc 99m Aggregated Albumin / blood
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Technetium Tc 99m Aggregated Albumin / pharmacokinetics
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Time Factors
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Transforming Growth Factor beta / blood*
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Transforming Growth Factor beta / pharmacokinetics*
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Transforming Growth Factor beta / therapeutic use
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Transforming Growth Factor beta1
Substances
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Membrane Lipids
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Technetium Tc 99m Aggregated Albumin
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Tgfb1 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1