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Blood-brain barrier permeability measurements by double-indicator method using intravenous injection
G M Knudsen1, K D Pettigrew, C S Patlak
1Department of Neurology, University Clinic Rigshospitalet, Copenhagen, Denmark.
The American Journal of Physiology
|March 1, 1994
Summary
A new intravenous method accurately estimates blood-brain barrier transfer rates, matching traditional intracarotid techniques for substances like D-glucose and L-phenylalanine. This offers a less invasive approach for studying brain barrier permeability.
Area of Science:
- Neuroscience
- Physiology
- Pharmacokinetics
Background:
- The double-indicator technique with intracarotid bolus injection is established for estimating human blood-brain barrier transfer rates.
- Accurate measurement of blood-brain barrier permeability is crucial for understanding neurological disorders and drug delivery.
Purpose of the Study:
- To develop and validate a less invasive method using intravenous tracer injection for blood-brain barrier transfer rate estimation.
- To compare the accuracy of the new intravenous technique with the established intracarotid bolus injection method.
Main Methods:
- A novel method involves peripheral arterial input and jugular vein output measurements.
- A five-parameter Dirac impulse response models cerebrovascular passage, correcting for substance input differences.
- This model is combined with a brain capillary model and convoluted with the test substance's arterial input curve.
Main Results:
- The intravenous technique yielded results comparable to the intracarotid method for D-glucose transfer.
- Similar agreement was observed for L-phenylalanine when the erythrocyte compartment was considered.
- Intravenous data for leucine and water also corroborated previous intracarotid findings.
Conclusions:
- The developed intravenous tracer injection method provides a reliable and less invasive alternative for assessing blood-brain barrier permeability.
- This technique simplifies the estimation of transfer rates for various substances across the human blood-brain barrier.
- The findings support the broader applicability of intravenous injections for pharmacokinetic studies of the brain.