European Journal of Applied Physiology

, Volume 113, Issue 8, pp 1909–1917 | Cite as

Cerebrovascular autoregulation: lessons learned from spaceflight research

  • Andrew P. Blaber
  • Kathryn A. Zuj
  • Nandu Goswami
Invited Review


This review summarizes our current understanding of cerebral blood flow regulation with exposure to microgravity, outlines potential mechanisms associated with post-flight orthostatic intolerance, and proposes future directions for research and linkages with cerebrovascular disorders found in the general population. It encompasses research from cellular mechanisms (e.g. hind limb suspension: tissue, animal studies) to whole body analysis with respect to understanding human responses using space analogue studies (bed rest, parabolic flight) as well as data collected before, during, and after spaceflight. Recent evidence indicates that cerebrovascular autoregulation may be impaired in some astronauts leading to increased susceptibility to syncope upon return to a gravitational environment. The proposed review not only provides insights into the mechanisms of post-flight orthostatic intolerance, but also increases our understanding of the mechanisms associated with pathophysiological conditions (e.g. unexplained syncope) with clinical applications in relation to postural hypotension or intradialytic hypotension.


Gender Post-flight orthostatic intolerance Bed rest Parabolic flights Spinal cord injury 


  1. Aaslid R, Lindegaard KF, Sorteberg W, Nornes H (1989) Cerebral autoregulation dynamics in humans. Stroke 20:45–52PubMedCrossRefGoogle Scholar
  2. Arbeille P, Sigaudo D, Le Traon AP, Herault S, Porcher M, Gharib C (1998) Femoral to cerebral arterial blood flow redistribution and femoral vein distension during orthostatic: tests after 4 days in the head-down tilt position or confinement. Eur J Appl Physiol 78:208–218CrossRefGoogle Scholar
  3. Arbeille P, Fomina G, Roumy J, Alferova I, Tobal N, Herault S (2001) Adaptation of the left heart, cerebral and femoral arteries, and jugular and femoral veins during short- and long-term head-down tilt and spaceflights. Eur J Appl Physiol 86:157–168PubMedCrossRefGoogle Scholar
  4. Bagian JP, Hackett P (1991) Cerebral blood flow—comparison of ground-based and spaceflight data and correlation with space adaptation syndrome. J Clin Pharmacol 31:1036–1040PubMedCrossRefGoogle Scholar
  5. Bellapart J, Fraser JF (2009) Transcranial doppler assessment of cerebral autoregulation. Ultrasound Med Biol 35:883–893PubMedCrossRefGoogle Scholar
  6. Blaber AP, Bondar RL, Stein F, Dunphy PT, Moradshahi P, Kassam MS, Freeman R (1997) Transfer function analysis of cerebral autoregulation dynamics in autonomic failure patients. Stroke 28:1686–1692PubMedCrossRefGoogle Scholar
  7. Blaber AP, Goswami N, Bondar RL, Kassam MS (2011) Impairment of cerebral blood flow regulation in astronauts with orthostatic intolerance after flight. Stroke 42:1844–1850PubMedCrossRefGoogle Scholar
  8. Blaber AP, Hinghofer-Szalkay H, Goswami N (2012) Blood volume redistribution during hypovolemia. Aviat Space Environ Med. (in press)Google Scholar
  9. Bondar RL, Stein F, Vaitkus PJ, Johnston KW, Chadwick LC, Norris JW (1990) Transcranial doppler studies of flow velocity in middle cerebral-artery in weightlessness. J Clin Pharmacol 30:390–395PubMedCrossRefGoogle Scholar
  10. Buckey JC, Lane LD, Levine BD, Watenpaugh DE, Wright SJ, Moore WE (1996) Orthostatic intolerance after spaceflight. J Appl Physiol 81:7–18PubMedGoogle Scholar
  11. Catz A, Bluvshtein V, Korczyn AD, Pinhas I, Gelernter I, Nissel T, Vered Y, Bornstein NM, Akselrod S (2007) Modified cold pressor test by cold application to the foot after spinal cord injury: suggestion of hemodynamic control by the spinal cord. Am J Phys Med Rehabil 86:875–882PubMedCrossRefGoogle Scholar
  12. Catz A, Bluvshtein V, Pinhas I, Akselrod S, Gelernter I, Nissel T, Vered Y, Bornstein N, Korczyn AD (2008) Cold pressor test in tetraplegia and paraplegia suggests an independent role of the thoracic spinal cord in the hemodynamic responses to cold. Spinal Cord 46:33–38PubMedCrossRefGoogle Scholar
  13. Chillon JM, Baumbach GL (2002) Autoregulation: Arterial and intracranial pressure. In: Edvinsson L, Krause DN (eds) Cerebral blood flow and metabolism. Lippincott Williams & Wilkins, Philadelphia, pp 395–412Google Scholar
  14. Chiquet C, Custaud MA, Le Traon AP, Millet C, Gharib C, Denis P (2003) Changes in intraocular pressure during prolonged (7-day) head-down tilt bed rest. J Glaucoma 12:204–208PubMedCrossRefGoogle Scholar
  15. Claydon VE, Steeves JD, Krassioukov A (2006) Orthostatic hypotension following spinal cord injury: understanding clinical pathophysiology. Spinal Cord 44:341–351PubMedCrossRefGoogle Scholar
  16. Davis MJ, Hill MA (1999) Signalling mechanisms underlying the vascular myogenic response. Physiological Rev 79:387–423Google Scholar
  17. Deegan BM, Sorond FA, Lipsitz LA, Olaighin G, Serrador JM (2009) Gender related differences in cerebral autoregulation in older healthy subjects. Conf Proc IEEE Eng Med Biol Soc 1:2859–2862Google Scholar
  18. Deegan BM, Devine ER, Geraghty MC, Jones E, Olaighin G, Serrador JM (2010) The relationship between cardiac output and dynamic cerebral autoregulation in humans. J Appl Physiol 109:1424–1431PubMedCrossRefGoogle Scholar
  19. Dineen NE, Brodie FG, Robinson TG, Panerai RB (2010) Continuous estimates of dynamic cerebral autoregulation during transient hypocapnia and hypercapnia. J Appl Physiol 108:604–613PubMedCrossRefGoogle Scholar
  20. Draeger J, Schwartz R, Groenhoff S, Stern C (1995) Self-tonometry under microgravity conditions. Aviat Space Environ Med 66:568–570PubMedGoogle Scholar
  21. Edgell H, Robertson AD, Hughson RL (2012) Hemodynamics and brain blood flow during posture change in younger women and postmenopausal women compared with age-matched men. J Appl Physiol 112:1482–1493PubMedCrossRefGoogle Scholar
  22. Edvinsson L (1990) Innervation of the cerebral vasculature and its functional significance. In: Harper AM, Jennett S (eds) Cerebral blood flow and metabolism. Manchester University Press, Manchester, pp 22–47Google Scholar
  23. Edwards MR, Shoemaker JK, Hughson RL (2002) Dynamic modulation of cerebrovascular resistance as an index of autoregulation under tilt and controlled PETCO2. Am J Physiol Regul Integr Comp Physiol 283:R653–R662PubMedGoogle Scholar
  24. Edwards MR, Topor ZL, Hughson RL (2003) A new two-breath technique for extracting the cerebrovascular response to arterial carbon dioxide. Am J Physiol Regul Integr Comp Physiol 284:R853–R859PubMedGoogle Scholar
  25. Edwards MR, Devitt DL, Hughson RL (2004) Two-breath CO2 test detects altered dynamic cerebrovascular autoregulation and CO2 responsiveness with changes in arterial PCO2. Am J Physiol Regul Integr Comp Physiol 287:R627–R632PubMedCrossRefGoogle Scholar
  26. Fogarty J (2011) Risk of microgravity-induced visual alterations/intracranial pressure (ICP). NASA Human Research Roadmap [On-line].
  27. Franco Folino A (2007) Cerebral autoregulation and syncope. Prog Cardiovasc Dis 50:49–80PubMedCrossRefGoogle Scholar
  28. Frey MAB, Mader TH, Bagian JP, Charles JB, Meehan RT (1993) Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt. J Appl Physiol 74:319–325PubMedGoogle Scholar
  29. Fu Q, Levine BD, Pawelczyk JA, Ertl AC, Diedrich A, Cox JF, Zuckerman JH, Ray CA, Smith ML, Iwase S, Saito M, Sugiyama Y, Mano T, Zhang R, Iwasaki K, Lane LD, Buckey JC Jr, Cooke WH, Robertson RM, Baisch FJ, Blomqvist CG, Eckberg DL, Robertson D, Biaggionib I (2002) Cardiovascular and sympathetic neural responses to handgrip and cold pressor stimuli in humans before, during and after spaceflight. J Physiol 544:653–664PubMedCrossRefGoogle Scholar
  30. Geary GG, Krause DN, Purdy RE, Duckles SP (1998) Simulated microgravity increases myogenic tone in rat cerebral arteries. J Appl Physiol 85:1615–1621PubMedGoogle Scholar
  31. Gonzalez F, Chang JY, Banovac K, Messina D, Martinez-Arizala A, Kelley RE (1991) Autoregulation of cerebral blood flow in patients with orthostatic hypotension after spinal cord injury. Paraplegia 29:1–7PubMedCrossRefGoogle Scholar
  32. Goswami N, Batzel JJ, Clément G, Stein TP, Hargens AR, Sharp MK, Blaber AP, Roma PG, Hinghofer-Szalkay HG (2012) Maximizing information from space data resources: a case for expanding integration across research disciplines. Eur J Appl Physiol. 2012 Oct 17. [Epub ahead of print]Google Scholar
  33. Gulbenkian S, Uddman R, Edvinsson L (2001) Neuronal messengers in the human cerebral circulation. Peptides 22:995–1007PubMedCrossRefGoogle Scholar
  34. Hainsworth R (2004) Pathophysiology of syncope. Clin Auton Res 14:18–24PubMedCrossRefGoogle Scholar
  35. Hamel E (2006) Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol 100:1059–1064PubMedCrossRefGoogle Scholar
  36. Handrakis JP, DeMeersman RE, Rosado-Rivera D, LaFountaine MF, Spungen AM, Bauman WA, Wecht JM (2009) Effect of hypotensive challenge on systemic hemodynamics and cerebral blood flow in persons with tetraplegia. Clin Auton Res 19:39–45PubMedCrossRefGoogle Scholar
  37. Hargens AR, Watenpaugh DE (1996) Cardiovascular adaptation to spaceflight. Med Sci Sports Exercise 28:977–982CrossRefGoogle Scholar
  38. Harm DL, Jennings RT, Meck JV, Powell MR, Putcha L, Sams CP, Schneider SM, Shackelford LC, Smith SM, Whitson PA (2001) Genome and hormones: gender differences in physiology—invited review: gender issues related to spaceflight: a NASA perspective. J Appl Physiol 291:2374–2383Google Scholar
  39. Harper AM (1990) Physiological control of the cerebral circulation. In: Harper AM, Jennett S (eds) Cerebral blood flow and metabolism. Manchester University Press, Manchester, pp 4–26Google Scholar
  40. Hirayanagi K, Iwase S, Kamiya A, Watanabe Y, Shiozawa T, Yamaguchi N (2005) Alternations of static cerebral and systemic circulation in normal humans during 14-day head-down bed rest. Med Sci Monit 11:CR570–CR575PubMedGoogle Scholar
  41. Houtman S, Colier WN, Oeseburg B, Hopman MT (2000) Systemic circulation and cerebral oxygenation during head-up tilt in spinal cord injured individuals. Spinal Cord 38:158–163PubMedCrossRefGoogle Scholar
  42. Houtman S, Serrador JM, Colier WN, Strijbos DW, Shoemaker K, Hopman MT (2001) Changes in cerebral oxygenation and blood flow during lbnp in spinal cord-injured individuals. J Appl Physiol 91:2199–2204PubMedGoogle Scholar
  43. Hughson RL, Edwards MR, O’Leary DD, Shoemaker JK (2001) Critical analysis of cerebrovascular autoregulation during repeated head up tilt. Stroke 32:2403–2408PubMedCrossRefGoogle Scholar
  44. Iwasaki KI, Levine BD, Zhang R, Zuckerman JH, Pawelczyk JA, Diedrich A, Ertl AC, Cox JF, Cooke WH, Giller CA, Ray CA, Lane LD, Buckey JC, Baisch FJ, Eckberg DL, Robertson D, Biaggioni I, Blomqvist CG (2007) Human cerebral autoregulation before, during and after spaceflight. J Physiol-London 579:799–810PubMedCrossRefGoogle Scholar
  45. Kastrup A, Thomas C, Hartmann C, Schabet M (1997) Sex dependency of cerebrovascular CO2 reactivity in normal subjects. Stroke 28:2353–2356PubMedCrossRefGoogle Scholar
  46. Kawai Y, Murthy G, Watenpaugh DE, Breit GA, Deroshia CW, Hargens AR (1993) Cerebral blood flow velocity in humans exposed to 24-h of head-down tilt. J Appl Physiol 74:3046–3051PubMedGoogle Scholar
  47. Kirsch KA, Baartz FJ, Gunga HC, Rocker L (1993) Fluid shifts into and out of superficial tissues under microgravity and terrestrial conditions. Clin Investig 71:687–689PubMedCrossRefGoogle Scholar
  48. Kramer LA, Sargsyan AE, Hasan KM, Polk JD, Hamilton DR (2012) Orbital and intracranial effects of microgravity: findings at 3-T MR imaging. Radiology 263:819–827PubMedCrossRefGoogle Scholar
  49. Lakin WD, Stevens SA, Penar PL (2007) Modeling intracranial pressures in microgravity: the influence of the blood-brain barrier. Aviat Space Environ Med 78:932–936PubMedCrossRefGoogle Scholar
  50. Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, Smith SM, Lane HW, Krauhs JM (1996) Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol 81(1):105–116PubMedGoogle Scholar
  51. Levine BD, Pawelczyk JA, Ertl AC, Cox JF, Zuckerman JH, Diedrich A, Biaggioni I, Ray CA, Smith ML, Iwase S, Saito M, Sugiyama Y, Mano T, Zhang R, Iwasaki K, Lane LD, Buckey JC, Cooke WH, Baisch FJ, Robertson D, Eckberg DL, Blomqvist CG (2002) Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight. J Physiol (London) 538:331–340CrossRefGoogle Scholar
  52. Mader TH, Gibson C, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Duc T, Lipsky W, Choi J, Stern C, Kuyumjian R, Paulson OB (2011) Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118:2058–2069PubMedCrossRefGoogle Scholar
  53. Mano T (2005) Autonomic neural functions in space. Curr Pharmaceutical Biotechnol 6:319–324CrossRefGoogle Scholar
  54. Mathias CJ (2006) Orthostatic hypotension and paroxysmal hypertension in humans with high spinal cord injury. Prog Brain Res 152:231–243PubMedCrossRefGoogle Scholar
  55. Mitsis GD, Poulin MJ, Robbins PA, Marmarelis VZ (2004) Nonlinear modeling of the dynamic effects of arterial pressure and CO2 variations on cerebral blood flow in healthy humans. IEEE Trans Biomed Eng 51:1932–1943PubMedCrossRefGoogle Scholar
  56. Nanda RN, Wyper DJ, Johnson RH, Harper AM (1976) The effect of hypocapnia and change of blood pressure on cerebral blood flow in men with cervical spinal cord transection. J Neurol Sci 30:129–135PubMedCrossRefGoogle Scholar
  57. NASA (2011) The Visual Impairment and Intracranial Pressure Summit ReportGoogle Scholar
  58. Panerai RB (1998) Assessment of cerebral pressure autorgeulation in humans- a review of measurement methods. Physiol Meas 19:305–338PubMedCrossRefGoogle Scholar
  59. Panerai RB, Dineen N, Brodie F, Robinson T (2010) Spontaneous fluctuations in cerebral blood flow regulation: contribution of PaCO2. J Appl Physiol 109:1860–1868PubMedCrossRefGoogle Scholar
  60. Panerai RB, Salinet AS, Robinson TG (2012) Contribution of arterial blood pressure and PaCO2 to the cerebrovascular response to motor stimulation. Am J Physiol Heart Circ Physiol 302:H459–H466PubMedCrossRefGoogle Scholar
  61. Paulson OB, Strandgaard S, Edvinsson L (1990) Cerebral autoregulation. Cerebrovasc Brain Metab Rev 2:161–192PubMedGoogle Scholar
  62. Pavy-Le Traon A, Costes-Salon MC, Vasseur-Clausen P, Bareille MP, Maillet A, Parant M (2002) Changes in kinetics of cerebral autoregulation with head-down bed rest. Clin Physiol Funct Imaging 22:108–114CrossRefGoogle Scholar
  63. Polk JD (2009) “Flight Surgeon Perspective: Gaps in Human Health, Performance, and Safety,” presentation to Committee of the Decadal Survey on Biological and Physical Sciences in Space, August. National Research Council, Washington, D.C., USAGoogle Scholar
  64. Prisby RD, Wilkerson MK, Sokoya EM, Bryan RM, Wilson E, Delp MD (2006) Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms. J Appl Physiol 101:348–353PubMedCrossRefGoogle Scholar
  65. Strandgaard S, Paulson OB (1984) Cerebral autoregulation. Stroke 15:413–416PubMedCrossRefGoogle Scholar
  66. Sun XQ, Yao YJ, Yang CB, Jiang SZ, Jiang CL, Liang WB (2005) Effect of lower-body negative pressure on cerebral blood flow velocity during 21 days head-down tilt bed rest. Med Sci Monit 11:CR1–CR5PubMedGoogle Scholar
  67. Suzuki H, Takanashi J, Kobayashi K, Nagasawa K, Tashima K, Kohno Y (2001) MR imaging of idiopathic intracranial hypertension. AJNR 22:196–199PubMedGoogle Scholar
  68. Taneja I, Moran C, Medow MS, Glover JL, Montgomery LD, Stewart JM (2007) Differential effects of lower body negative pressure and upright tilt on splanchnic blood volume. Am J Physiol Heart Circ Physiol 292:H1420–H1426PubMedCrossRefGoogle Scholar
  69. Tontisirin N, Muangman SL, Suz P, Pihoker C, Fisk D, Moore A, Lam AM, Vavilala MS (2007) Early childhood gender differences in anterior and posterior cerebral blood flow velocity and autoregulation. Pediatrics 119:e610–e615PubMedCrossRefGoogle Scholar
  70. Vavilala MS, Kincaid MS, Muangman SL, Suz P, Rozet I, Lam AM (2005) Gender differences in cerebral blood flow velocity and autoregulation between the anterior and posterior circulations in healthy children. Pediatr Res 58:574–578PubMedCrossRefGoogle Scholar
  71. Wahl M, Schilling L (1993) Regulation of cerebral blood flow-a brief review. Acta Neurochir Suppl (Wien) 59:3–10Google Scholar
  72. Waters WW, Ziegler MG, Meck JV (2002) Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance. J Appl Physiol 92:586–594PubMedGoogle Scholar
  73. Wilkerson MK, Muller-Delp J, Colleran PN, Delp MD (1999) Effects of hindlimb unloading on rat cerebral, splenic, and mesenteric resistance artery morphology. J Appl Physiol 87:2115–2121PubMedGoogle Scholar
  74. Wilkerson MK, Colleran PN, Delp MD (2002) Acute and chronic head-down tail suspension diminishes cerebral perfusion in rats. Am J Physiol Heart Circ Physiol 282:H328–H334PubMedGoogle Scholar
  75. Wilkerson MK, Lesniewski LA, Golding EM, Bryan RM, Amin A, Wilson E (2005) Simulated microgravity enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism. Am J Physiol Heart Circ Physiol 288:H1652–H1661PubMedCrossRefGoogle Scholar
  76. Wilson LC, Cotter JD, Fan JL, Lucas RA, Thomas KN, Ainslie PN (2010) Cerebrovascular reactivity and dynamic autoregulation in tetraplegia. Am J Physiol Regul Integr Comp Physiol 298:R1035–R1042PubMedCrossRefGoogle Scholar
  77. Wilson MH, Imray CHE, Hargens AR (2011) The Headache of high altitude and microgravity—Similarities with clinical syndromes of cerebral venous hypertension. High Altitude Med Biol 12:379–386. doi: 10.1089/ham.2011.1026 CrossRefGoogle Scholar
  78. Yamamoto M, Meyer JS, Sakai F, Jakoby R (1980) Effect of differential spinal cord transection on human cerebral blood flow. J Neurol Sci 47:395–406PubMedCrossRefGoogle Scholar
  79. Zhang R, Zuckerman JH, Pawelczyk JA, Levine BD (1997) Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress. J Appl Physiol 83:2139–2145PubMedGoogle Scholar
  80. Zhang LN, Zhang LF, Ma J (2001) Simulated microgravity enhances vasoconstrictor responsiveness of rat basilar artery. J Appl Physiol 90:2296–2305PubMedCrossRefGoogle Scholar
  81. Zuj KA, Arbeille P, Shoemaker JK, Blaber AP, Greaves DK, Xu D, Hughson RL (2012) Impaired cerebrovascular autoregulation and reduced CO2 reactivity after long duration spaceflight. Am J Physiol Heart Circ Physiol 302:H2592–H2598PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Andrew P. Blaber
    • 1
  • Kathryn A. Zuj
    • 2
  • Nandu Goswami
    • 3
  1. 1.Aerospace Physiology Laboratory, Department of Biomedical Physiology and KinesiologySimon Fraser UniversityBurnabyCanada
  2. 2.Cardiovascular Dynamics Laboratory, Department of KinesiologyUniversity of WaterlooWaterlooCanada
  3. 3.Institute of PhysiologyMedical University GrazGrazAustria

Personalised recommendations