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1. Introduction
2. Outline
3. Introduction to the assessment of brain delivery
4. Factors affecting brain delivery and exchange
5. Blood-brain barrier transport assumptions
6. Common issues to be addressed
7. Solute choice and assay
8. Animal and disease state
9. Overview of brain transport kinetics
10. Simple two compartment model for brain transport
11. Kinetic equations for two compartment model
12. Initial uptake assumptions
13. Unidiractional uptake simplification
14. Initial uptake analysis and k(in) determination
15. Kinetic constants
16. Conversion of k(in) to PS and IP
17. Brain vascular correction
18. Capillary depletion
19. Steady state distribution
20. Example of brain distribution volume
21. In vivo methods to asses BBB transport
22. In situ brain perfusion method
23. Getting started - requiered equipment
24. Perfusion set up
25. Perfusion fluid
26. Perfusion fluid rate
27. What is the optimum infusion rate?
28. BBB integrity: PS brain perfusion vs. in vivo
29. Differences revealed by perfusion vs. in vivo
30. Measurement of flow
31. Brain uptake of flow markers
32. Systemic (iv) administration method
33. iv administration method for brain uptake
34. Calculation for initial uptake
35. External analysis
36. Limitations of iv administration method
37. Brain microdialysis method
38. Microdialysis approach
39. Data analysis
40. Microdialysis limitations
41. Brain efflux index (BEI) method
42. Illustration of brain efflux index method
43. Brain efflux calculation
44. Pros and cons of BEI method
45. Summary
46. Acknowledgements

Topics Covered

• Common issues in brain uptake assessment
• Multiple factors impact brain delivery and exchange
• Assumptions
• What information is sought?
• What brain compartment is appropriate?
• Brain transport kinetics
• In vivo methods to assess BBB transport
• In situ brain perfusion method
• Systemic (IV) administration method
• Brain microdialysis method
• Brain efflux index (BEI) method

Links

Series:

• The Blood-Brain Barrier

Categories:

• Methods
• Neuroscience
• Pharmaceutical Sciences

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on March 1, 2008
• Archived on May 31, 2018

Financial Disclosures

• Prof. Quentin Smith has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.