Transport of brain-derived neurotrophic factor across the blood-brain barrier

Brain-derived neurotrophic factor (BDNF is a potential therapeutic agent fo r degenerative disorders of the central nervous system. In this report, we investigated the ability of BDNF to cross the blood-brain barrier (BHK). BD NF; was stable in blood up to 60 min after i.v. injection, with evidence fo r aggregation, and had an early, rapid influx into brain. By 10 min, most o f the BDNF sequestered by the cerebral cortex was associated with the paren chyma rather than with the endothelial cells, demonstrating complete passag e across the BBB. A small dose of unlabeled BDNF enhanced the entry of I-12 5-BDNF from blood to brain after all i.v. bolus injection, whereas larger c loses had no effect. In contrast, a large dose of unlabeled BDNF inhibited the influx of I-125-BDNF: during in situ brain perfusion. After intracerebr oventricular injection. the efflux of BDNF from brain to blood occurred at a rats similar to that for reabsorption of cerebrospinal fluid. and no evid ence for self-inhibition was found. Therefore, we conclude that intact BDNF in the peripheral circulation crosses the BBB by a high-capacity. saturabl e transport system. (C) 1998 Elsevier Science Ltd. Ali rights reserved.