Introduction to the Blood-Brain Barrier Methodology, Biology and Pathology

The blood-brain barrier serves to protect the brain from toxic substances whilst simultaneously allowing access to essential nutrients and chemical signals. At the interface between brain and body, knowledge of the blood-brain barrier forms an essential component in the complete understanding of a large proportion of medical disciplines. Nevertheless, it seems that ignorance of both the biology of this important membrane and the methodology suitable for its investigation still remains an impediment to progress in many fields, including, for example, the development of new and efficacious neuropharmaceuticals, cerebrovascular disease, Alzheimer's disease, cerebral AIDS and brain tumours. This introduction for both researchers and clinicians across the medical sciences is intended to aid both those beginning work directly in this area and those wishing simply to be better informed when interpreting information where the blood-brain barrier may be involved. Advances in both methodology and biology are detailed in 50 chapters from international authorities.

List of contributors; 1. Blood-brain barrier methodology and biology; Part I. Methodology: 2. The carotid artery single injection technique; 3. Development of the Brain Efflux Index (BEI) method and its application to the blood-brain barrier efflux transport study; 4. In situ brain perfusion; 5. Intravenous injection/pharmacokinetics; 6. Isolated brain capillaries: an in vitro model of blood-brain barrier research; 7. Isolation and behavior of plasma membrane vesicles made from cerebral capillary endothelial cells; 8. Patch clamp technique with isolated brain microvessel membranes; 9. Tissue culture of brain endothelial cells - induction of blood-brain barrier properties by brain factors; 10. Brain microvessel endothelial cell culture systems; 11. Intracerebral microdialysis; 12. Blood-brain barrier permeability measured with histochemistry; 13. Measuring local cerebral capillary permeability-surface area products by quantitative autoradiography; 14. Measurement of blood-brain barrier permeability in humans using indicator diffusion; 15. Measurement of blood-brain barrier permeability in humans with positron emission tomography; 16. Magnetic resonance imaging of blood-brain barrier permeability; 17. Molecular biology of brain capillaries; Part II. Transport Biology: 18. Biology of the blood-brain glucose transporter; 19. Glucose transporters in mammalian brain development; 20. Blood-brain barrier amino acid transport; 21. P-glycoprotein, a guardian of the brain; 22. Blood-brain barrier ion transport; 23. Ion channels in endothelial cells; 24. Interactions of lipoproteins with the blood-brain barrier; 25. Fatty acid and lipid intermediate transport; 26. Blood-brain barrier transport of drugs; Part III. General Aspects of CNS Transport: 27. The blood-CSF barrier and the choroid plexus; 28. Arachnoid membrane, subarachnoid CSF and pia-glia; 29. Circumventricular organs of the brain; 30. Transport in the developing brain; Part IV. Signal Transduction/Biochemical Aspects: 31. Regulation of brain endothelial cell tight junction permeability; 32. Chemotherapy and chemosensitization; 33. Lipid composition of brain microvessels; 34. Brain microvessel antigens; 35. Molecular dissection of tight junctions: occludin and ZO-1; 36. Phosphatidylinositol pathways; 37. Nitric oxide and endothelin at the blood-brain barrier; 38. Role of intracellular calcium in regulation of brain endothelial permeability; 39. Cytokines and the blood-brain barrier; 40. Blood-brain barrier and monoamines, revisited; Part V. Pathophysiology in Disease States: 41. Cerebral amyloid angiopathy; 42. Brain microvasculature in multiple sclerosis; 43. Hemostasis and the blood-brain barrier; 44. Microvascular pathology in cerebrovascular ischemia; 45. HIV infection and the blood-brain barrier; 46. Hypertension; 47. The blood-brain barrier in brain tumours; 48. The pathophysiology of blood-brain barrier dysfunction due to traumatic brain injury; 49. Cerebral malaria and the brain microvasculature; 50. Molecular basis of tissue tropism of bacterial meningitis.

A comprehensive introduction to the blood-brain barrier and methodology of its study which will be an important information resource for a wide range of medical specialists from researcher to clinician. Advances in both methodology and biology of the blood-brain barrier are detailed in 50 chapters from international authorities.