Transport of brain-derived neurotrophic factor across the blood-brain barrier.
Level 5 - mechanism / opinion, no new human data
Preclinical laboratory and animal physiological study without human data.
PubMed 9886678 · doi:10.1016/s0028-3908(98)00141-5
What was done
The authors evaluated the blood-brain barrier (BBB) penetration of radioiodinated brain-derived neurotrophic factor (125I-BDNF). They measured plasma stability and brain influx kinetics following intravenous (i.v.) injection, evaluated parenchymal versus endothelial sequestration in the cerebral cortex at 10 minutes, tested competition effects with unlabeled BDNF via i.v. bolus and in situ brain perfusion, and assessed brain-to-blood clearance kinetics following intracerebroventricular injection.
What was found
The abstract does not report exact numerical values or sample sizes. BDNF remained stable in blood for up to 60 minutes after i.v. injection (with signs of aggregation) and demonstrated rapid initial entry into the brain, with most cortical BDNF localized to the parenchyma rather than endothelial cells by 10 minutes. A low dose of unlabeled BDNF enhanced 125I-BDNF brain uptake after i.v. bolus, while higher doses showed no effect; in contrast, a large dose of unlabeled BDNF inhibited influx during in situ brain perfusion. Brain-to-blood efflux after intracerebroventricular injection matched the rate of cerebrospinal fluid reabsorption without self-inhibition.
Why it matters
This study provides mechanistic evidence that intact BDNF in the circulation can cross the blood-brain barrier into brain tissue via a high-capacity, saturable transport mechanism. This supports the potential viability of systemic delivery routes for neurotrophin-based CNS therapeutics.
Limits
The abstract omits sample sizes, quantitative pharmacokinetic parameters, and explicit species details. Findings from preclinical animal perfusion models may not directly translate to human blood-brain barrier transport kinetics or achieve therapeutic concentrations in pathological states.
Cited by
- contradicts Circulating BDNF does not cross the blood-brain barrier into the brain.