TGFalpha and the blood-brain barrier: accumulation in cerebral vasculature

Transforming growth factor alpha (TGFalpha) 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 TGFalpha (18). In this report, we studied the passage of TGFalpha from blood to brain after an i.v. bolus injection. Using radioactively labeled peptide, we found that TGFalpha had an apparent rate of entry of 0.7 microl/g/min. However, most of the TGFalpha was trapped in the capillary endothelial cells of the cerebral vasculature rather than entering the brain parenchyma. No saturation was detected. TGFalpha was relatively stable in blood for 20 min after i.v. injection, but dissociation of the isotope 125I was more evident in brain. The accumulation of TGFalpha in the cerebral vasculature was similar to that of amyloid-beta protein1-40. Therefore, we conclude that TGFalpha from the periphery interacts with the blood-brain barrier without substantial uptake into brain parenchyma. This raises the possibility that TGFalpha might be involved in intracranial vascular disorders such as angiopathy.