PMID- 9886678
OWN - NLM
STAT- MEDLINE
DCOM- 19990323
LR  - 20230921
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 37
IP  - 12
DP  - 1998 Dec
TI  - Transport of brain-derived neurotrophic factor across the blood-brain barrier.
PG  - 1553-61
AB  - Brain-derived neurotrophic factor (BDNF) is a potential therapeutic agent for 
      degenerative disorders of the central nervous system. In this report, we 
      investigated the ability of BDNF to cross the blood-brain barrier (BBB). BDNF was 
      stable in blood up to 60 min after i.v. injection, with evidence for aggregation, 
      and had an early, rapid influx into brain. By 10 min, most of the BDNF 
      sequestered by the cerebral cortex was associated with the parenchyma rather than 
      with the endothelial cells, demonstrating complete passage across the BBB. A 
      small dose of unlabeled BDNF enhanced the entry of 125I-BDNF from blood to brain 
      after an i.v. bolus injection, whereas larger doses had no effect. In contrast, a 
      large dose of unlabeled BDNF inhibited the influx of 125I-BDNF during in situ 
      brain perfusion. After intracerebroventricular injection, the efflux of BDNF from 
      brain to blood occurred at a rate similar to that for reabsorption of 
      cerebrospinal fluid, and no evidence for self-inhibition was found. Therefore, we 
      conclude that intact BDNF in the peripheral circulation crosses the BBB by a 
      high-capacity, saturable transport system.
FAU - Pan, W
AU  - Pan W
AD  - VA Medical Center, New Orleans, LA 70112-1262, USA. wpan@mailhost.tcs.tulane.edu
FAU - Banks, W A
AU  - Banks WA
FAU - Fasold, M B
AU  - Fasold MB
FAU - Bluth, J
AU  - Bluth J
FAU - Kastin, A J
AU  - Kastin AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Technetium Tc 99m Aggregated Albumin)
SB  - IM
MH  - Animals
MH  - *Blood-Brain Barrier
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacokinetics
MH  - Capillaries/physiology
MH  - Cerebrovascular Circulation/physiology
MH  - Humans
MH  - Injections, Intravenous
MH  - Iodine Radioisotopes/pharmacokinetics
MH  - Kinetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Recombinant Proteins/pharmacokinetics
MH  - Regression Analysis
MH  - Technetium Tc 99m Aggregated Albumin/pharmacokinetics
MH  - Time Factors
EDAT- 1999/01/14 00:00
MHDA- 1999/01/14 00:01
CRDT- 1999/01/14 00:00
PHST- 1999/01/14 00:00 [pubmed]
PHST- 1999/01/14 00:01 [medline]
PHST- 1999/01/14 00:00 [entrez]
AID - S0028390898001415 [pii]
AID - 10.1016/s0028-3908(98)00141-5 [doi]
PST - ppublish
SO  - Neuropharmacology. 1998 Dec;37(12):1553-61. doi: 10.1016/s0028-3908(98)00141-5.