Permeability of the blood–brain barrier to neurotrophins

• Published in: Brain research 1998-03, Vol.788 (1), p.87-94
• Main Authors: Pan, Weihong, Banks, William A, Kastin, Abba J
• Format: Article
• Language: English
• Subjects: 1-Octanol; Acids; Animals; Biological and medical sciences; Blood-Brain Barrier - physiology; Blood–brain barrier; Brain; Brain - metabolism; Buffers; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Chemical Precipitation; Drug Stability; Fundamental and applied biological sciences. Psychology; Lipids - chemistry; Male; Mice; Mice, Inbred ICR; Nerve Growth Factors - pharmacokinetics; Neurotrophin; Phosphates; Solubility; Spinal cord; Spinal Cord - metabolism; Tissue Distribution; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(97)01525-4

To evaluate the feasibility of applying blood-borne neurotrophins to promote normal function of the central nervous system (CNS) and to rescue neuronal degeneration, we characterized the permeability of the blood–brain barrier (BBB) to neurotrophins. We report here that some members of the neurotrophin family (NGF, βNGF, NT3, and NT5) can cross the BBB of mice in vivo to arrive at the brain parenchyma. BBB permeability differed among individual neurotrophins in that NGF had the fastest influx rate ( K i) and NT3 the slowest, and that the entry rate of NGF was twice that of its smaller bioactive subunit βNGF. BBB permeability also differed at various CNS regions in that the cervical spinal cord had the greatest rate of influx, whereas brain had the lowest. Saturability of influx was suggested by self-inhibition studies for NT3 in vivo, and for NGF in an in situ brain perfusion system, indicating the presence of saturable transport systems. The results suggest that peripheral administration of neurotrophins could have therapeutic effects within the CNS.