THE MULTIDRUG-RESISTANCE P-GLYCOPROTEIN (PGP, MDR1) IS AN EARLY MARKER OF BLOOD-BRAIN-BARRIER DEVELOPMENT IN THE MICROVESSELS OF THE DEVELOPING HUMAN BRAIN

The multidrug-resistance P-glycoprotein (Pgp) was initially identified as an energy-dependent proton pump, which transports a variety of non -related compounds out of chemotherapy-resistant cancer cells. Molecul ar biological investigations using knockout mice for the mouse homolog ue of the human Pgp showed that these mice partially lack a functionin g blood-brain barrier, indicating that Pgp has an important role in th e blood-brain barrier as its normal function. The presence of Pgp expr ession in formalin-fixed and wax-processed tissue sections can be asse ssed using the monoclonal antibody, JSB-1. Since no data on the develo pmental expression of Pgp are available, we stained a developmental se ries of human brain sections with JSB-1. Our results indicate that Pgp expression in endothelia of brain microvessels occurs regularly in em bryos of about 30-mm crown-rump length (CRL). Strong reactivity is see n in blood vessels of fetuses from 123-mm CRL. There is also reactivit y in pial blood vessels but not in choroid plexus blood vessels known to be without a blood-brain barrier. Pgp expression is therefore an ea rly marker of the blood-brain barrier in the developing human brain.