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1. Introduction
2. Outline
3. Neurotrophins and their receptors
4. Characteristics of neurotrophins
5. Neurotrophin receptors and signals
6. Other neurotrophic proteins
7. Neurotrophic peptides (naturally occurring)
8. Neurotrophic support to the brain and spinal cord
9. Blood-brain barrier and blood-spinal cord barrier
10. Characteristics of the blood-brain barrier
11. NGF 30 minutes after iv injection
12. Comparison of neurotrophins kinetic data
13. Octanol/PBS partition coefficient
14. Capillary depletion 10 minutes after iv
15. Saturable transport of NGF
16. Saturable transport of NT3
17. BDNF 60 minutes after iv
18. BDNF entering brain parenchyma
19. Saturable transport of BDNF
20. Efflux of BDNF
21. Classical neurotrophins
22. GDNF 30 minutes after iv administration
23. Influx of GDNF
24. GDNF is relatively stable in circulation
25. Influx transport of CNTF
26. CNTF degradation assay
27. CNTF - conclusion
28. LIF
29. LIF mainly shows reversible vascular binding
30. LIF influx is a saturable process
31. Kinetics of LIF influx in the spinal cord
32. Examination of LIF influx by in situ brain perfusion
33. Blocking antibody, but not CNTF, inhibits LIF influx
34. LIF: no efflux transport
35. Growth hormone: lack of saturable transport
36. In situ brain perfusion data for the growth hormone
37. Growth hormone: uptake by brain parenchyma
38. Co-injection of insulin and growth hormone
39. Insulin does not interfere with IGF1 transport
40. Inhibition of IGF-1 transport by insulin
41. EGF: example of a neurotrophic peptide
42. Recovery of EGF from brain after iv administration
43. EGF distribution between brain and blood
44. TGFalpha shares the transport system with EGF
45. Anti-EGFR Ab showed no effect on EGF influx
46. EGFR knock-out mice maintain transport function
47. There is no efflux transport system for EGF
48. Enhancing CNS delivery of peptides and proteins
49. BBB-targeting of BDNF in rats
50. Neuroprotective effect of bFGF/OX26-SA conjugate
51. Application of a BBB-penetrating form of GDNF
52. Effects of IGF-I intranasal administration
53. Left forepaw-placing test
54. Vestibulomotor function in the beam balance test
55. BDNF gene delivery into the CNS
56. BDNF levels in transplanted mouse brain cells
57. Limitations
58. Other means for neuroprotection and regeneration
59. Summary
60. References

Topics Covered

• Overview of neurotrophins
• CNS physiology and roles in neuroregeneration
• The blood-brain barrier (BBB)
• General strategies to enhance CNS delivery
• Progress on neurotrophin delivery across the BBB
• Limitations and future directions

Links

Series:

• The Blood-Brain Barrier

Categories:

• Neuroscience
• Pharmaceutical Sciences

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on March 1, 2008
• Archived on January 31, 2017

Financial Disclosures

• Professor Weihong Pan has no commercial/financial relationships to disclose