Regulation of cerebral blood flow and metabolism during exercise

What is the topic of this review? The manuscript collectively combines the experimental observations from >100 publications focusing on the regulation of cerebral blood flow and metabolism during exercise from 1945 to the present day. What advances does it highlight? This article highlights the importance of traditional and historical assessments of cerebral blood flow and metabolism during exercise, as well as traditional and new insights into the complex factors involved in the integrative regulation of brain blood flow and metabolism during exercise. The overarching theme is the importance of quantifying cerebral blood flow and metabolism during exercise using techniques that consider multiple volumetric cerebral haemodynamics (i.e. velocity, diameter, shear and flow).

[1]  Tianne Numan,et al.  Static autoregulation in humans: a review and reanalysis. , 2014, Medical engineering & physics.

[2]  P. Rasmussen,et al.  The cerebral metabolic ratio is not affected by oxygen availability during maximal exercise in humans , 2008, The Journal of physiology.

[3]  C. Owman,et al.  Adrenergic innervation of pial arteries related to the circle of Willis in the cat. , 1967, Brain research.

[4]  K. Pattinson,et al.  Effect of exercise on cerebral perfusion in humans at high altitude. , 2005, Journal of applied physiology.

[5]  N. AinsliePhilip,et al.  Cerebral Blood Flow at High Altitude , 2014 .

[6]  B. Groves,et al.  Internal carotid flow velocity with exercise before and after acclimatization to 4,300 m. , 1991, Journal of applied physiology.

[7]  N. Wahlgren,et al.  Physical exercise increases middle cerebral artery blood flow velocity , 2004, Neurosurgical Review.

[8]  P. Raven,et al.  The effect of changes in cardiac output on middle cerebral artery mean blood velocity at rest and during exercise , 2005, The Journal of physiology.

[9]  S. Lucas,et al.  High-Intensity Interval Exercise and Cerebrovascular Health: Curiosity, Cause, and Consequence , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  N. Secher,et al.  The effects of normoxia, hypoxia, and hyperoxia on cerebral haemoglobin saturation using near infrared spectroscopy during maximal exercise , 2010 .

[11]  G. Nylin,et al.  The behaviour of the cerebral circulation during muscular exercise. , 1962, Acta physiologica Scandinavica.

[12]  P. Ainslie,et al.  Effect of acute hypoxia on regional cerebral blood flow: effect of sympathetic nerve activity. , 2014, Journal of applied physiology.

[13]  Andrew C. Dimmen,et al.  Cerebral blood flow and oxygenation at maximal exercise: The effect of clamping carbon dioxide , 2011, Respiratory Physiology & Neurobiology.

[14]  J. Bevan,et al.  Sympathetic control of cerebral arteries: specialization in receptor type, reserve, affinity, and distribution , 1987, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  D. Attwell,et al.  Glial and neuronal control of brain blood flow , 2022 .

[16]  Philip N. Ainslie,et al.  Sympathetic control of the brain circulation: Appreciating the complexities to better understand the controversy , 2017, Autonomic Neuroscience.

[17]  J. Gati,et al.  Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia. , 2014, Journal of applied physiology.

[18]  Eric A Newman,et al.  Functional Hyperemia and Mechanisms of Neurovascular Coupling in the Retinal Vasculature , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  N. Lassen,et al.  Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise. , 1993, Journal of applied physiology.

[20]  N. Secher,et al.  Muscle Tensing During Standing: Effects on Cerebral Tissue Oxygenation and Cerebral Artery Blood Velocity , 2001, Stroke.

[21]  Philip N. Ainslie,et al.  Why is the neural control of cerebral autoregulation so controversial? , 2014, F1000prime reports.

[22]  P. Raven,et al.  α1‐Adrenergic receptor control of the cerebral vasculature in humans at rest and during exercise , 2013, Experimental physiology.

[23]  E Rosow,et al.  Simultaneous determination of the accuracy and precision of closed-circuit cardiac output rebreathing techniques. , 2007, Journal of applied physiology.

[24]  M. Haykowsky,et al.  Resting and exercise cerebral blood flow in long-term heart transplant recipients. , 2012, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[25]  L. Rowell Human Cardiovascular Control , 1993 .

[26]  J. Ulatowski,et al.  Cerebrovascular response to decreased hematocrit: effect of cell-free hemoglobin, plasma viscosity, and CO2. , 2003, American journal of physiology. Heart and circulatory physiology.

[27]  James Duffin,et al.  Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing: mechanisms of regulation, measurement, and interpretation. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.

[28]  D. O'Leary,et al.  Corticospinal excitability is associated with hypocapnia but not changes in cerebral blood flow , 2016, The Journal of physiology.

[29]  N. Secher,et al.  Cerebral carbohydrate cost of physical exertion in humans. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[30]  Steven Laureys,et al.  The Effect of Clonidine Infusion on Distribution of Regional Cerebral Blood Flow in Volunteers , 2008, Anesthesia and Analgesia.

[31]  P. Ainslie,et al.  Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise. , 2016, Journal of applied physiology.

[32]  Shigehiko Ogoh,et al.  The distribution of blood flow in the carotid and vertebral arteries during dynamic exercise in humans , 2011, The Journal of physiology.

[33]  R. Naeije,et al.  Relationship of middle cerebral artery blood flow velocity to intensity during dynamic exercise in normal subjects , 2004, European Journal of Applied Physiology and Occupational Physiology.

[34]  Joseph A Fisher,et al.  Integrative regulation of human brain blood flow , 2014, The Journal of physiology.

[35]  K. Klausen,et al.  Effects of hyperoxia on leg blood flow and metabolism during exercise. , 1977, Journal of applied physiology: respiratory, environmental and exercise physiology.

[36]  P. Ainslie,et al.  Hypoxemia, oxygen content, and the regulation of cerebral blood flow. , 2016, American journal of physiology. Regulatory, integrative and comparative physiology.

[37]  J. Mitchell,et al.  Cerebral blood flow during submaximal and maximal dynamic exercise in humans. , 1989, Journal of applied physiology.

[38]  Y. Tzeng,et al.  Cerebrovascular Regulation During Transient Hypotension and Hypertension in Humans , 2010, Hypertension.

[39]  M. van Buchem,et al.  Middle cerebral artery diameter changes during rhythmic handgrip exercise in humans , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[40]  N. Secher,et al.  Blood Lactate is an Important Energy Source for the Human Brain , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  Grant R. Gordon,et al.  Brain metabolism dictates the polarity of astrocyte control over arterioles , 2008, Nature.

[42]  P. Ainslie,et al.  Regional cerebral blood flow in humans at high altitude: gradual ascent and 2 wk at 5,050 m. , 2014, Journal of applied physiology.

[43]  N. Secher,et al.  Syncope, cerebral perfusion, and oxygenation. , 2003, Journal of applied physiology.

[44]  H. Handa,et al.  Characterization of beta adrenergic receptors in human cerebral arteries and alteration of the receptors after subarachnoid hemorrhage. , 1986, Stroke.

[45]  Albert Dahan,et al.  Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI. , 2014, Journal of applied physiology.

[46]  P. Ainslie,et al.  Hypercapnia is essential to reduce the cerebral oxidative metabolism during extreme apnea in humans , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[47]  H. Wolff,et al.  CEREBRAL CIRCULATION: III. THE VASOMOTOR CONTROL OF CEREBRAL VESSELS , 1928 .

[48]  B. Kayser,et al.  The Effect of Adding CO2 to Hypoxic Inspired Gas on Cerebral Blood Flow Velocity and Breathing during Incremental Exercise , 2013, PloS one.

[49]  Xiangrong Shi,et al.  Cerebral autoregulation is preserved during orthostatic stress superimposed with systemic hypotension. , 2006, Journal of applied physiology.

[50]  N. Secher,et al.  Hypoxia and exercise provoke both lactate release and lactate oxidation by the human brain , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[51]  N. Secher,et al.  Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals , 2013, The Journal of physiology.

[52]  N. Secher,et al.  Regional cerebral artery mean flow velocity and blood flow during dynamic exercise in humans. , 1992, Journal of applied physiology.

[53]  Leif Østergaard,et al.  The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[54]  Y. Tzeng,et al.  Aging blunts hyperventilation-induced hypocapnia and reduction in cerebral blood flow velocity during maximal exercise , 2011, AGE.

[55]  R. Jacobs,et al.  Hypocapnia during hypoxic exercise and its impact on cerebral oxygenation, ventilation and maximal whole body O2 uptake , 2013, Respiratory Physiology & Neurobiology.

[56]  Philip N. Ainslie,et al.  Blood pressure regulation IX: cerebral autoregulation under blood pressure challenges , 2013, European Journal of Applied Physiology.

[57]  N. Secher,et al.  Dehydration affects cerebral blood flow but not its metabolic rate for oxygen during maximal exercise in trained humans , 2014, The Journal of physiology.

[58]  N. Wahlgren,et al.  Carotid artery blood flow and middle cerebral artery blood flow velocity during physical exercise. , 1996, Journal of applied physiology.

[59]  N. Secher,et al.  Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise , 2011, The Journal of physiology.

[60]  Olaf B. Paulson,et al.  Unchanged Cerebral Blood Flow and Oxidative Metabolism after Acclimatization to High Altitude , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[61]  M. Matsumoto,et al.  Carbondioxide reactivity of the blood flow in human basilar artery estimated by the transcranial Doppler method in normal men: a comparison with that of the middle cerebral artery. , 1988, Ultrasound in medicine & biology.

[62]  S. Ogoh,et al.  Differential blood flow responses to CO2 in human internal and external carotid and vertebral arteries , 2012, The Journal of physiology.

[63]  C. Lundby,et al.  Cerebral glucose and lactate consumption during cerebral activation by physical activity in humans , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[64]  A. Subudhi,et al.  Cerebrovascular responses to incremental exercise during hypobaric hypoxia: effect of oxygenation on maximal performance. , 2008, American journal of physiology. Heart and circulatory physiology.

[65]  Rong Zhang,et al.  Middle cerebral artery flow velocity and pulse pressure during dynamic exercise in humans. , 2005, American journal of physiology. Heart and circulatory physiology.

[66]  N. Secher,et al.  Lactate, glucose and O2 uptake in human brain during recovery from maximal exercise , 2000, The Journal of physiology.

[67]  A. Subudhi,et al.  Cerebral blood flow at high altitude. , 2014, High altitude medicine & biology.

[68]  R. Hughson,et al.  Cerebral hemodynamics and resistance exercise. , 2002, Medicine and science in sports and exercise.

[69]  Bernhard Neundörfer,et al.  Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation , 2003, Journal of the Neurological Sciences.

[70]  F F SAVERIO,et al.  [Cerebral circulation]. , 1954, Omnia therapeutica. Supplemento.

[71]  Nicolas Caesar Petersen,et al.  Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans , 2010, The Journal of physiology.

[72]  A. Subudhi,et al.  Frontal and motor cortex oxygenation during maximal exercise in normoxia and hypoxia. , 2009, Journal of applied physiology.

[73]  K Ide,et al.  Cerebral metabolic response to submaximal exercise. , 1999, Journal of applied physiology.

[74]  M. Stembridge,et al.  Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia , 2016, The Journal of physiology.

[75]  N. Eves,et al.  Regional cerebral blood flow distribution during exercise: Influence of oxygen , 2012, Respiratory Physiology & Neurobiology.

[76]  S. Ogoh,et al.  Alterations in cerebral autoregulation and cerebral blood flow velocity during acute hypoxia: rest and exercise. , 2007, American journal of physiology. Heart and circulatory physiology.

[77]  D. J. Cunningham,et al.  The effects on the respiration and performance during exercise of adding oxygen to the inspired air , 1954, The Journal of physiology.

[78]  N. Secher,et al.  Association between fatigue and failure to preserve cerebral energy turnover during prolonged exercise. , 2003, Acta physiologica Scandinavica.

[79]  A. Thorstensson,et al.  Effect of changes in arterial oxygen content on circulation and physical performance. , 1975, Journal of applied physiology.

[80]  R. Wise,et al.  Using High-Field Magnetic Resonance Imaging to Estimate Distensibility of the Middle Cerebral Artery , 2016, Neurodegenerative Diseases.

[81]  C. Lundby,et al.  Cerebral blood flow, frontal lobe oxygenation and intra-arterial blood pressure during sprint exercise in normoxia and severe acute hypoxia in humans , 2018, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[82]  P. Raven,et al.  Autonomic neural control of heart rate during dynamic exercise: revisited , 2014, The Journal of physiology.

[83]  E. Mackenzie,et al.  Effects of Decreasing Arterial Blood Pressure on Cerebral Blood Flow in the Baboon: INFLUENCE OF THE SYMPATHETIC NERVOUS SYSTEM , 1975, Circulation research.

[84]  K. Herholz,et al.  Regional cerebral blood flow in man at rest and during exercise , 2004, Journal of Neurology.

[85]  Xavier Golay,et al.  Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia—an ultrasound and MRI study , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[86]  Y. Tzeng,et al.  Regional brain blood flow in man during acute changes in arterial blood gases , 2012, The Journal of physiology.

[87]  P. Scheinberg,et al.  Cerebral circulation and metabolism in pulmonary emphysema and fibrosis with observations on the effects of mild exercise. , 1953, The Journal of clinical investigation.

[88]  E. Asmussen,et al.  Studies on the Regulation of Respiration in Heavy Work , 1946 .

[89]  Philip N. Ainslie,et al.  Influence of Changes in Blood Pressure on Cerebral Perfusion and Oxygenation , 2010, Hypertension.

[90]  C. Lambertsen,et al.  Respiratory and cerebral circulatory control during exercise at .21 and 2.0 atmospheres inspired p02. , 1959, Journal of applied physiology.

[91]  Andrew C. Dimmen,et al.  Does cerebral oxygen delivery limit incremental exercise performance? , 2011, Journal of applied physiology.

[92]  L. Jorfeldt,et al.  Determination of human leg blood flow: a thermodilution technique based on femoral venous bolus injection. , 1978, Clinical science and molecular medicine.

[93]  J. Donnelly,et al.  Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery , 2014, The Journal of physiology.

[94]  P. Scheinberg,et al.  Effects of vigorous physical exercise on cerebral circulation and metabolism. , 1954, The American journal of medicine.

[95]  A. Gelb,et al.  Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans , 2015, Anesthesiology.

[96]  N. Secher,et al.  Phenylephrine decreases frontal lobe oxygenation at rest but not during moderately intense exercise. , 2010, Journal of applied physiology.

[97]  N. Secher,et al.  Experimental Physiology –Research Paper: Glycopyrrolate abolishes the exercise‐induced increase in cerebral perfusion in humans , 2010, Experimental physiology.

[98]  N. Secher,et al.  Middle cerebral artery blood velocity during exercise with beta-1 adrenergic and unilateral stellate ganglion blockade in humans. , 2000, Acta physiologica Scandinavica.

[99]  E. Croteau,et al.  Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease , 2016, Annals of the New York Academy of Sciences.

[100]  C. Howarth,et al.  The contribution of astrocytes to the regulation of cerebral blood flow , 2014, Front. Neurosci..

[101]  E. Croteau,et al.  Brain and systemic glucose metabolism in the healthy elderly following fish oil supplementation. , 2011, Prostaglandins, leukotrienes, and essential fatty acids.

[102]  P. Fadel,et al.  Autonomic adjustments to exercise in humans. , 2015, Comprehensive Physiology.

[103]  N. Secher,et al.  A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain , 2004, The Journal of physiology.

[104]  Can Ozan Tan,et al.  Relative Contributions of Sympathetic, Cholinergic, and Myogenic Mechanisms to Cerebral Autoregulation , 2014, Stroke.

[105]  W. Lennox,et al.  CEREBRAL CIRCULATION: XII. THE EFFECT ON PIAL VESSELS OF VARIATIONS IN THE OXYGEN AND CARBON DIOXIDE CONTENT OF THE BLOOD , 1930 .

[106]  S. Ogawa,et al.  Central Hypervolemia with Hemodilution Impairs Dynamic Cerebral Autoregulation , 2007, Anesthesia and analgesia.

[107]  N. Secher,et al.  Middle cerebral artery flow velocity and blood flow during exercise and muscle ischemia in humans. , 1992, Journal of applied physiology.

[108]  N. Secher,et al.  Non‐selective β‐adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans , 2008, The Journal of physiology.

[109]  N. Secher,et al.  Middle cerebral artery blood velocity during rowing. , 1997, Acta physiologica Scandinavica.

[110]  Christopher J. Marley,et al.  Acute Exercise Stress Reveals Cerebrovascular Benefits Associated with Moderate Gains in Cardiorespiratory Fitness , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[111]  M. Amann,et al.  Autonomic responses to exercise: Group III/IV muscle afferents and fatigue , 2015, Autonomic Neuroscience.

[112]  P. Scheinberg Cerebral blood flow in vascular disease of the brain; with observations on the effects of stellate ganglion block. , 1950, The American journal of medicine.

[113]  P. Ainslie,et al.  Evidence for hysteresis in the cerebral pressure-flow relationship in healthy men. , 2017, American journal of physiology. Heart and circulatory physiology.