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How does blood flow inform us about brain function?

How does blood flow inform us about brain function?. Cerebrovascular anatomy & neural regulation of CNS blood flow Neurovascular coupling. HST 583 Brad Dickerson, M.D. bradd@nmr.mgh.harvard.edu. How does blood flow inform us about brain function?.

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How does blood flow inform us about brain function?

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  1. How does blood flow inform us about brain function? Cerebrovascular anatomy & neural regulation of CNS blood flow Neurovascular coupling HST 583 Brad Dickerson, M.D. bradd@nmr.mgh.harvard.edu

  2. How does blood flow inform us about brain function? Cerebrovascular anatomy & neural regulation of CNS blood flow Cerebral blood flow: intro Cerebrovascular anatomy Neurotransmitter systems & neural regulation

  3. Blood flow and the organ of thought “…blood supply to any part of the cerebral tissue is varied in accordance with the activity of the chemiccal changes which underlie the functional action of that part…” -- Roy & Sherrington, 1890 “We must suppose a very delicate adjustment whereby the circulation follows the needs of the cerebral activity. Blood very likely may rush to each region of the cortex according as it is most active, but of this we know nothing.” -- W. James, 1890

  4. Blood flow and the organ of thought Slide courtesy of M. Raichle

  5. Blood flow and the organ of thought • The brain requires blood for: • General support of maintenance functions, like every organ - requires energy (ATP) • Specific localized support of functional activity related to neural activity - requires energy (ATP) • Blood supplies substrates for energy production: Glucose and oxygen • ~750 ml/min

  6. The route of blood to the head

  7. The route of blood within the head

  8. 10 mm Circle of Willis

  9. The route of blood within the head

  10. T1 T2

  11. The route of blood within the head

  12. The route of blood within the head

  13. Scale of the circulatory system Aorta: 2.5 cm (~1 in) Large arteries (e.g., carotid): .5 - 1 cm Arterioles: 10 - 50 um Capillaries: 5 - 10 um (RBC)

  14. Scale of the circulatory system Large arteries (e.g., carotid): .5 - 1 cm Arterioles: 10 - 50 um

  15. Scale of the circulatory system Capillaries: 5 - 10 um (RBC)

  16. Scale of the circulatory system Venules/veins

  17. The route of blood within the head

  18. The route of blood within the head

  19. The route of blood within the head

  20. The route of blood within the head

  21. Pial arteriolar anastomoses 1 mm From Edvinsson, 1993

  22. AP view: Vertebral artery angiogram

  23. Cortical capillary vasculature 5 mm

  24. Cortical neural structure 5 mm

  25. Cortical capillary vasculature Grey matter has 2-4 times the capillary density of white matter 5 mm

  26. Cerebellar Vasculature

  27. Inferior Olivary Nucleus and Inferior Cerebellar Peduncle 2 mm From Duvernoy, 1995

  28. Cerebellar Histology Blue = myelin Pink = neuropil 1 mm From Duvernoy, 1995

  29. 100 mm 500 mm From Duvernoy, 1995

  30. Cerebellar Cortical Histology

  31. 50 mm Cerebellar histology and vascularization Molecular Layer Purkinje Cells Granular Layer From Duvernoy, 1995

  32. Capillary density in rat brain is proportional to metabolic rate High levels of CMRglu Cochlear nucleus, mammillary body, cortex High levels of CBF Cochlear nucleus, mammillary body, cortex Low levels of CMRglu Hypothalamus, cerebellum, medulla Low levels of CBF Hypothalamus, cerebellum, medulla From Edvinsson, 1993

  33. Flow of CSF

  34. CSF return to venous blood

  35. Large vessels in subarachnoid space

  36. Blood Brain Barrier • What cerebral capillaries have: • Tight continuous quintuple-layered intercellular junctions • low wall thickness (0.2 um) • higher mitochondrial content • thick basement membrane • What cerebral capillaries don’t have: • fenestrations • lots of vesicles • fluid-filled bulk transport channels

  37. Blood Brain Barrier • Allows passage/transport of small molecules (H2O, O2, CO2), lipophilic molecules (EtOH, heroin), passive transport of glucose, active transport of amino acids/NT precursors • Prevents passage of larger molecules (dopamine), charged molecules, etc

  38. Measurement of blood flow to the brain • Aorta 90cm/s, ICA 40cm/s, arterioles 10-250mm/s, capillaries 1mm/s • Transcranial doppler ultrasound

  39. Cerebral autoregulation • CBF remains constant over wide range of change in arterial pressure

  40. Flow is regulated by arteriolar smooth muscle Arterioles: 10 - 50 um

  41. Sites of CBF Regulation • Large diameter vessels (ANS) • Smaller diameter arterioles, venules (neurogenic) • Must have smooth muscle with appropriate innervation and receptor site to act upon • If signaling is at capillary level, message must move upstream to supplying arteriole

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