Permeability of the blood-brain barrier to neurotrophins.
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, betaNGF, 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 (Ki) and NT3 the slowest, and that the entry rate of NGF was twice that of its smaller bioactive subunit betaNGF. 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.
Pan
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VA Medical Center, New Orleans, LA 70146, USA. wpan@mailhost.tcs.tulane.edu
Banks
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Kastin
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D020003:1-Octanol; D000143:Acids; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002021:Buffers; D011232:Chemical Precipitation; D004355:Drug Stability; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009414:Nerve Growth Factors / Q000493:pharmacokinetics*; D010710:Phosphates; D012995:Solubility; D013116:Spinal Cord / Q000378:metabolism*; D014018:Tissue Distribution
D000143:Acids; D002021:Buffers; D008055:Lipids; D009414:Nerve Growth Factors; D010710:Phosphates; D020003:1-Octanol