Abstract
Stroke is a pathophysiological condition which results in alterations in cerebral
blood flow (CBF). The mechanism by which the brain maintains adequate CBF in presence
of fluctuating cerebral perfusion pressure (CPP) is known as cerebral autoregulation
(CA). Disturbances in CA may be influenced by a number of physiological pathways including
the autonomic nervous system (ANS). The cerebrovascular system is innervated by adrenergic
and cholinergic nerve fibers. The role of the ANS in regulating CBF is widely disputed
owing to several factors including the complexity of the ANS and cerebrovascular interactions,
limitations to measurements, variation in methods to assess the ANS in relation to
CBF as well as experimental approaches that can or cannot provide insight into the
sympathetic control of CBF. CA is known to be impaired in stroke however the number
of studies investigating the mechanisms by which this occurs are limited. This literature
review will focus on highlighting the assessment of the ANS and CBF via indices derived
from the analyses of heart rate variability (HRV), and baroreflex sensitivity (BRS),
and providing a summary of both clinical and animal model studies investigating the
role of the ANS in influencing CA in stroke. Understanding the mechanisms by which
the ANS influences CBF in stroke patients may provide the foundation for novel therapeutic
approaches to improve functional outcomes in stroke patients.
Keywords
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References
- Asymmetric dynamic cerebral autoregulatory response to cyclic stimuli.Stroke. 2007; 38: 1465-1469
- Why is the neural control of cerebral autoregulation so controversial?.F1000prime Rep. 2014; 6: 14
- Stability of cerebral metabolism and substrate availability in humans during hypoxia and hyperoxia.Clin. Sci. (Lond.). 2013; 126 (Advance online publication): 661-670
- Disorders of the autonomic nervous system after hemispheric cerebrovascular disorders: an update.J. Vasc. Interv. Neurol. 2015; 8: 43-52
- Diagnosis and management of autonomic dysfunction in dementia syndromes.Curr. Treat. Options Neurol. 2019; 21: 38
- Impaired circadian heart rate variability in Parkinson’s disease: a time-domain analysis in ambulatory setting.BMC Neurol. 2020; 20: 152
- Low dose beta blockade in acute stroke ("BEST" trial): an evaluation.Br. Med. J. (Clin. Res. Ed.). 1988; 296: 737-741
- The central autonomic network: functional organization, dysfunction, and perspective.Mayo Clin. Proc. 1993; 68: 988-1001
- Addition of 24-hour heart rate variability parameters to the cardiovascular health study stroke risk score and prediction of incident stroke: the cardiovascular health study.J. Am. Heart Assoc. 2017; 6
- Phenylephrine decreases frontal lobe oxygenation at rest but not during moderately intense exercise.J. Appl. Physiol. 2010; 108: 1472-1478
- Sympathetic control of the brain circulation: appreciating the complexities to better understand the controversy.Auton. Neurosci. 2017; 207: 37-47
- Eicosanoid synthesis elicited by norepinephrine in piglet parietal cortex.Brain Res. 1987; 403: 243-248
- Targeting the autonomic nervous system for risk stratification, outcome prediction and neuromodulation in ischemic stroke.Int. J. Mol. Sci. 2021; : 22
- Autonomic dysfunction in essential hypertension: a systematic review.Ann. Med. Surg. 2014; 3: 2-7
- Sympathetic nerve activity in the superior cervical ganglia increases in response to imposed increases in arterial pressure.Am. J. Phys. Regul. Integr. Comp. Phys. 2008; 294: R1255-R1261
- Cerebral sympathetic nerve activity has a major regulatory role in the cerebral circulation in REM sleep.J. Appl. Physiol. 2009; 1985: 1050-1056
- Autonomic dysfunction affects dynamic cerebral autoregulation during Valsalva maneuver: comparison between healthy and autonomic dysfunction subjects.J. Appl. Physiol. (1985). 2014; 117: 205-213https://doi.org/10.1152/japplphysiol.00893.2013
- Autonomic dysfunction affects dynamic cerebral autoregulation during valsalva maneuver: comparison between healthy and autonomic dysfunction subjects.J. Appl. Physiol. 2014; 117: 205-213
- Inconsistent relation of nonlinear heart rate variability indices to increasing vagal tone in healthy humans.Auton. Neurosci. 2018; 213: 1-7
- Relationship between ischemic stroke location and autonomic cardiac function.J. Clin. Neurosci. 2013; 20: 406-409
- Autonomic dysfunction in Parkinson’s disease: implications for pathophysiology, diagnosis, and treatment.Neurobiol. Dis. 2020; 134104700
- Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke.Stroke. 2005; 36: 1710-1715
- Parasympathetic autonomic dysfunction is common in mild cognitive impairment.Neurobiol. Aging. 2012; 33: 2324-2333
- Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence.Brain. 2003; 126: 2139-2152
- Orthostatic changes of cerebral blood flow velocity in patients with autonomic dysfunction.J. Neurol. Sci. 1991; 104: 32-38https://doi.org/10.1016/0022-510x(91)90212-p
- Dynamic but not static cerebral autoregulation is impaired in acute ischaemic stroke.Cerebrovasc. Dis. 2000; : 126-132
- Assessment of techniques used to evaluate the effect of posture and cardiac output on cerebral autoregulation.Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. 2008; : 1992-1995
- Cardiac sympathovagal modulation evaluated by short-term heart interval variability is subtly impaired in Alzheimer’s disease.Geriatr Gerontol Int. 2008; 8: 109-118
- Urinary incontinence after stroke.Stroke. 2007; 38: 2745-2751
- Beta-blockers reduce the risk of early death in ischemic stroke.J. Neurol. Sci. 2007; 252: 53-56
- Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke.J. Neurol. Neurosurg. Psychiatry. 2002; 72: 467-472
- Neurogenic mechanisms in the cerebrovascular bed. Autonomic nerves, amine receptors and their effects on cerebral blood flow.Acta Physiol. Scand. Suppl. 1975; 427: 1-35
- Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet Neurol. 2016; 15: 913-924
- Cerebral circulation II. Reaction of pial arteries to increase in blood pressure.Arch. Neurol. Psychiatr. 1939; 41: 9
- Cerebral circulation. The reaction of pial arteries to a fall in blood pressure.Arch. Neurol. Psychiatr. 1939; 37: 14
- Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.Clin. Auton. Res. 2011; 21: 69-72
- Heart rate variability and incident stroke: the atherosclerosis risk in communities study.Stroke. 2016; 47: 1452-1458
- Autonomic nervous system control of the cerebral circulation.Handb. Clin. Neurol. 2013; 117: 193-201
- Dynamic cerebrovascular autoregulation in patients prone to postural syncope: comparison of techniques assessing the autoregulation index from spontaneous variability series.Auton. Neurosci. 2022; 2022102920
- Cardiac vagus and exercise.Physiology (Bethesda). 2019; 34: 71-80
- Interaction of histamine with noradrenergic constrictory mechanisms in cat cerebral arteries and veins.Can. J. Physiol. Pharmacol. 1983; 61: 756-763
- Regional distribution of cerebral blood flow during exercise in dogs.J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 1980; 48: 213-217
- Intracranial pressure influences the level of sympathetic tone.Am. J. Physiol. Regul. Integr. Comp. Physiol. 2018; 315: R1049-R1053
- Perivascular nerves and the regulation of cerebrovascular tone.J. Appl. Physiol. (1985). 2006; 100: 1059-1064
- Sympathetic control of the cerebral vasculature in humans.Stroke. 2010; 41: 102-109
- Effects of sympathetic nerves on cerebral vessels in dog, cat, and monkey.Am. J. Phys. 1978; 235: H544-H552
- High NIHSS values predict impairment of cardiovascular autonomic control.Stroke. 2011; 42: 1528-1533
- Assessment of cerebral autoregulation in stroke: a systematic review and meta-analysis of studies at rest.J. Cereb. Blood Flow Metab. 2019; 39: 2105-2116
- The autonomic reflex screen in healthy participants from southwestern Ontario.Can. J. Neurol. Sci. 2013; 40: 848-853
- Changes in hemodynamics of the carotid and middle cerebral arteries before and after endoscopic sympathectomy in patients with palmar hyperhidrosis: preliminary results.J. Neurosurg. 1999; 90: 463-467https://doi.org/10.3171/jns.1999.90.3.0463
- Cardiovascular autonomic dysfunction after stroke.Neurol. Sci. 2021; 42: 1751-1758
- Early differentiation of dementia with lewy bodies and Alzheimer's disease: heart rate variability at mild cognitive impairment stage.Clin. Neurophysiol. 2018; 129: 1570-1578
- Cerebral blood flow regulation and neurovascular dysfunction in alzheimer disease.Nat. Rev. Neurosci. 2017; 18: 419-434
- Autonomic control of cerebral blood flow: fundamental comparisons between peripheral and cerebrovascular circulations in humans.J. Physiol. 2021; (Advance online publication)https://doi.org/10.1113/JP281058
- Incidence and outcome of orthostatic hypotension in stroke patients undergoing rehabilitation.Arch. Phys. Med. Rehabil. 2003; 84: 559-562
- Abnormal heart rate variability as a manifestation of autonomic dysfunction in hemispheric brain infarction.Stroke. 1996; 27: 2059-2063
- Autonomic nervous system disorders in stroke.Clin. Auton. Res. 1999; 9: 325-333
- Autonomic nervous dysfunction during acute cerebral infarction.Neurol. Res. 2010; 32: 821-827
- Assessing dynamic cerebral autoregulation after stroke using a novel technique of combining transcranial doppler ultrasonography and rhythmic handgrip.Blood Press. Monit. 2004; 9: 3-8
- Dynamic cerebral autoregulation measurement using rapid changes in head positioning: experiences in acute ischemic stroke and healthy control populations.Am. J. Physiol. Heart Circ. Physiol. 2019; 316: H673-H683https://doi.org/10.1152/ajpheart.00550.2018
- Physiology of cerebral blood flow.Br. J. Anaesth. 1976; 48: 719-734https://doi.org/10.1093/bja/48.8.719
- Comparison of static and dynamic cerebral autoregulation under anesthesia influence in a controlled animal model.PLoS One. 2021; 16 (Published 2021 Jan 8)e0245291https://doi.org/10.1371/journal.pone.0245291
- Protective effects of beta-blockers in cerebrovascular disease.Neurology. 2007; 68: 509-514
- Arterial baroreflex: a novel target for preventing stroke in rat hypertension.Stroke. 2007; 38: 1916-1923
- Sympathetic restraint of baroreflex control of heart period in normotensive and hypertensive subjects.Clin. Sci. (Lond.). 1994; 86: 547-556
- Preliminary study of dynamic cerebral autoregulation in acute ischemic stroke: association with clinical factors.Front. Neurol. 2018; 9 (Published 2018 Nov 26): 1006https://doi.org/10.3389/fneur.2018.01006
- Clonidine, moxonidine, folic acid, and mecobalamin improve baroreflex function in stroke-prone, spontaneously hypertensive rats.Acta Pharmacol. Sin. 2007; 28: 1550-1558
- Orthostatic hypotension: from pathophysiology to clinical applications and therapeutic considerations.J. Clin. Hypertens. (Greenwich). 2019; 21: 546-554
- Heart rate dynamics predict poststroke mortality.Neurology. 2004; 62: 1822-1826
- Clinical relevance of orthostatic hypotension in patients with atrial fibrillation and suspected transient ischemic attack. High blood press.Cardiovasc. Prev. 2020; 27: 93-101
- Autonomic function is impaired in elderly stroke survivors.Stroke. 2005; 36: 1026-1030
- Blood pressure variability and outcome in acute ischemic and hemorrhagic stroke: a post hoc analysis of the HeadPoST study.J. Hum. Hypertens. 2019; 33: 411-418
- Jugular venous overflow of noradrenaline from the brain: a neurochemical indicator of cerebrovascular sympathetic nerve activity in humans.J. Physiol. 2009; 587: 2589-2597
- Autonomic disturbances in acute cerebrovascular disease.Neurosci. Bull. 2019; 35: 133-144
- Biophysical characterization of the underappreciated and important relationship between heart rate variability and heart rate.Hypertension. 2014; 64: 1334-1343
- Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure.J. Am. Coll. Cardiol. 2000; 36: 1612-1618
- Metabolically active components of fat-free mass and resting energy expenditure in humans: recent lessons from imaging technologies.Obes. Rev. 2002; 3: 113-122
- Baroreflex and cerebral autoregulation are inversely correlated.Circ J. 2014; 78: 2460-2467https://doi.org/10.1253/circj.cj-14-0445
- Autonomic dysfunction in first ever ischemic stroke: prevalence, predictors and short term neurovascular outcome.Clin. Neurol. Neurosurg. 2016; 150: 54-58
- Autonomic dysfunction in mild cognitive impairment: evidence from power spectral analysis of heart rate variability in a cross-sectional case-control study.PLoS One. 2014; 9e96656
- Autonomic function in amnestic and non-amnestic mild cognitive impairment: spectral heart rate variability analysis provides evidence for a brain–heart axis.Sci. Rep. 2020; 10: 11661
- Cerebral autoregulation in ischemic stroke: from pathophysiology to clinical concepts.Brain Sci. 2021; 11: 511
- Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension.Biomed. Eng. Online. 2004; 3: 39
- Autonomic neural control of the cerebral vasculature: acute hypotension.Stroke. 2008; 39: 1979-1987
- Cerebral blood flow regulation and cognitive function: a role of arterial baroreflex function.J. Physiol. Sci. 2019; 69: 813-823
- Cerebral blood flow regulation and cognitive function: a role of arterial baroreflex function.J. Physiol. Sci. 2019; 69: 813-823https://doi.org/10.1007/s12576-019-00704-6
- Effect of an acute increase in central blood volume on cerebral hemodynamics.Am. J. Physiol. Regul. Integr. Comp. Physiol. 2015; 309: R902-R911
- Cardiovascular effects of human insular cortex stimulation.Neurology. 1992; 42: 1727-1732
- Cerebral Autoregulation: Control of Blood Flow in the Brain.1st ed. 2016
- Dynamic cerebral autoregulation in acute ischemic stroke assessed from spontaneous blood pressure fluctuations.Stroke. 2005; 36: 1684-1689https://doi.org/10.1161/01.STR.0000173183.36331.ee
- Functional sympatholysis during muscular activity. Observations on influence of carotid sinus on oxygen uptake.Circ. Res. 1962; 11: 370-380
- Cardiac baroreceptor sensitivity predicts long-term outcome after acute ischemic stroke.Stroke. 2003; 34: 705-712
- Cardiac baroreceptor sensitivity is impaired after acute stroke.Stroke. 1997; 28: 1671-1676
- The reciprocal relationship between cardiac baroreceptor sensitivity and cerebral autoregulation during simulated hemorrhage in humans.Auton. Neurosci. 2022; 241103007https://doi.org/10.1016/j.autneu.2022.103007
- Association between systemic inflammation, carotid arteriosclerosis, and autonomic dysfunction.Transl. Stroke Res. 2020; 11: 50-59
- Atrial fibrillation, stroke, and silent cerebrovascular disease: a population-based MRI study.Neurology. 2021; 97: e1608-e1619
- Baroreflex function in Parkinson's disease: insights from the modified-Oxford technique.J. Neurophysiol. 2020; 124: 1144-1151
- Does stroke subtype and measurement technique influence estimation of cerebral autoregulation in acute ischaemic stroke?.Cerebrovasc. Dis. 2013; 35: 257-261https://doi.org/10.1159/000347075
- A systematic review of cerebral hemodynamic responses to neural activation following stroke.J. Neurol. 2013; 260: 2715-2721
- Cerebral blood flow response to neural activation after acute ischemic stroke: a failure of myogenic regulation?.J. Neurol. 2013; 260: 2588-2595
- Nervous control of the cerebrovascular system: doubts and facts.Neurochem. Int. 1999; 35: 237-259
- Adrenergic regulation of innate immunity: a review.Front. Pharmacol. 2015; 6: 171
- Early rehabilitation after stroke: relationship between the heart rate variability and functional outcome.ESC Heart Fail. 2020; 7: 2983-2991
- Intracranial baroreflex yielding an early Cushing response in human.Acta Neurochir. Suppl. 2005; 95: 253-256https://doi.org/10.1007/3-211-32318-x_51
- Cerebral autoregulatory response depends on the direction of change in perfusion pressure.J. Neurotrauma. 2009; 26: 651-656
- Effects of induced hypertension on intracranial pressure and flow velocities of the middle cerebral arteries in patients with large hemispheric stroke.Stroke. 2002; 33: 998-1004
- Effects of body position on intracranial pressure and cerebral perfusion in patients with large hemispheric stroke.Stroke. 2002; 33: 497-501
- Is there an active mechanism limiting the influence of the sympathetic system on the cerebral vascular bed? Evidence for vasomotor escape from sympathetic stimulation in the rabbit.Brain Res. 1979; 164: 81-102
- The effect of bilateral stellectomy upon the cerebral circulation of man.J. Clin. Invest. 1951; 30: 90-93https://doi.org/10.1172/JCI102421
- Cervical sympathectomy on patients with occlusive cerebrovascular disease.Arch. Surg. 1969; 98: 317-320https://doi.org/10.1001/archsurg.1969.01340090093015
- Cardiovascular and neurological causes of sudden death after ischaemic stroke.Lancet Neurol. 2012; 11: 179-188
- Post-stroke cardiovascular complications and neurogenic cardiac injury: JACC state-of-the-art review.J. Am. Coll. Cardiol. 2020; 76: 2768-2785
- Post-stroke cardiovascular complications and neurogenic cardiac injury: JACC State-of-the-Art Review.J. Am. Coll. Cardiol. 2020; 76: 2768-2785
- Impaired baroreceptor reflex sensitivity in acute stroke is associated with insular involvement, but not with carotid atherosclerosis.Stroke. 2009; 40: 737-742
- Depressed baroreflex sensitivity in patients with Alzheimer's and Parkinson's disease.Neurobiol. Aging. 2001; 22: 435-438
- Stroke outcome prediction by blood pressure variability, heart rate variability, and baroreflex sensitivity.Stroke. 2020; 51: 1317-1320
- Sympathetic regulation of cerebral blood flow in humans: a review.Br. J. Anaesth. 2013; 111: 361-367
- Beat-to-beat blood pressure variability and heart rate variability in relation to autonomic dysregulation in patients with acute mild-moderate ischemic stroke.J. Clin. Neurosci. 2019; 64: 187-193
- Biphasic dose-dependent modulation of cardiac parasympathetic activity by moxonidine, an imidazoline I1-receptor agonist.J. Cardiovasc. Pharmacol. 2008; 52: 524-535
- Fundamental relationships between arterial baroreflex sensitivity and dynamic cerebral autoregulation in humans.J. Appl. Physiol. (1985). 2010; 108: 1162-1168https://doi.org/10.1152/japplphysiol.01390.2009
- Cerebrovascular regulation during transient hypotension and hypertension in humans.Hypertension. 2010; 56: 268-273
- Serum biomarkers and cerebral autoregulation as early warnings of delayed cerebral ischemia risk in patients after aneurysmal subarachnoid haemorrhage.J. Clin. Neurosci. 2021; 87: 35-43https://doi.org/10.1016/j.jocn.2021.02.009
- Effect of sympathetic nerve stimulation on cerebral blood flow in newborn piglets.Pediatr. Res. 1986; 20: 131-135
- Sympathetic reactivity of cerebral arteries in developing fetal lamb and adult sheep.Am. J. Phys. 1990; 258: H1432-H1438
- Insular stroke is associated with acute sympathetic hyperactivation and immunodepression.Eur. J. Neurol. 2013; 20: 153-159
- Autonomic imbalance and risk of dementia and stroke: the Framingham study.Stroke. 2021; 52: 2068-2076
- Reference values for resting blood flow to organs of man.Clin. Phys. Physiol. Meas. 1989; 10: 187-217
- Integrative regulation of human brain blood flow.J. Physiol. 2014; 592: 841-859
- Effects of insular involvement on functional outcome after intracerebral hemorrhage.Acta Neurol. Scand. 2021; 144: 559-565
- Distribution of cardiac output to the brain across the adult lifespan.J. Cereb. Blood Flow Metab. 2017; 37: 2848-2856https://doi.org/10.1177/0271678X16676826
- Comprehensive assessment for autonomic dysfunction in different phases after ischemic stroke.Int. J. Stroke. 2013; 8: 645-651
- Heart rate variability and baroreceptor sensitivity in acute stroke: a systematic review.Int. J. Stroke. 2015; 10: 796-800
- Autonomic neural control of dynamic cerebral autoregulation in humans.Circulation. 2002; 106: 1814-1820
Article info
Publication history
Published online: February 27, 2023
Accepted:
February 22,
2023
Received in revised form:
November 22,
2022
Received:
December 24,
2021
Identification
Copyright
© 2023 Published by Elsevier B.V.