TGFα and the blood-brain barrier:: Accumulation in cerebral vasculature

Transforming growth factor alpha (TGF alpha) is a cytokine that belongs to the epidermal growth factor (EGF) family of growth factors. EGF has a fast and saturable entry from blood to brain that is inhibitable by TGF alpha. (18). In this report, we studied the passage of TGF alpha from blood to brain after an i.v. bolus injection. Using radioactively labeled peptide, we found that TGF alpha had an apparent rate of entry of 0.7 mu l/g/min. However, most of the TGF alpha was trapped in the capillary endothelial cells of the cerebral vasculature rather than entering the brain parenchyma. No saturation was detected. TGF alpha was relatively stable in blood for 20 min after i.v. injection, but dissociation of the isotope I-125 was more evident in brain. The accumulation of TGF alpha in the cerebral vasculature was similar to that of amyloid-beta protein(1-40). Therefore, we conclude that TGF alpha from the periphery interacts with the blood-brain barrier without substantial uptake into brain parenchyma. This raises the possibility that TGF alpha might be involved in intracranial vascular disorders such as angiopathy. (C) 1999 Academic Press.