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Cerebral Autoregulation Mechanism | Report

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From: Biose Ifechukwude Joachim


Cerebral autoregulation (CA) is the multifactorial vascular mechanism that maintains a constant cerebral blood supply in spite of fluctuations in the cerebral perfusion pressure (CPP) (Lassen, 1959; Tiecks et al., 1995). This mechanism thrives for CPP values within the range of 50-150 mmHg (Lassen, 1959; Paulson, Strandgaard and Edvinsson, 1990; Panerai, 1998) (Fig. 1).

The vascular response involved in CA is rapid and so robust that hypertension (Eames et al., 2003; Serrador et al., 2005; Zhang et al., 2007) and aging (Eames et al., 2003; Fisher et al., 2008; Liu et al., 2013; Oudegeest-Sander et al., 2014) does not alter its physiological role.

However, CA is compromised following pathologic conditions such as traumatic brain injury, intracerebral haemorrhage, stroke, hyper-perfusion syndrome, and subarachnoid haemorrhage (Diedler et al., 2009; Atkins et al., 2010; Budohoski et al., 2012; Saeed et al., 2013; Buczek et al., 2013).

Fig. 1. Cerebral autoreglation in relation to vascular response. Within the upper and lower boundaries of the autoregulatory range (dotted lines), blood flow remains constant (blue line with beads). As Pressure falls below the lower limit, vascular smooth muscle relaxes to allow dilatation, while constriction of vessels (red circles) ensues to reduce blood flow as pressure approximates the upper limit. Adapted from Pires et al., 2013.


Based on factors affecting cerebral blood flow (CBF), CA can be classified into two categories, metabolic autoregulation (MA) and pressure autoregulation (PA).

Mainly due to changes in brain tissue pH (Cotev and Severinghaus, 1969; Betz and Heuser, 1967; Raichle, Posner and Plum, 1970), MA is the principal regulatory mechanism of CBF according to metabolic demand. This implies that MA responds to local or global ischemia and hypoxia which increases pH by increasing CBF via vasodilatation (Ekstrom-Jodal et al., 1971; Raichle and Stone, 1971).While PA is the vascular response to maintain blood flow following changes in perfusion pressure, achieved by varying the degree of vasoconstriction or vasodilatation of the cerebral vasculature.


In adults and under normal conditions, provided CPP falls within the boundary of 50-150 mmHg, CBF is preserved at approximately 50 mL per 100 g of brain tissue per minute (McHenry et al., 1974; Strandgaard et al., 1976; Paulson, Strandgaard and Edvinsson, 1990). Outside this range of CPP, CA is impaired and CBF becomes directly dependent on mean arterial pressure (MacKenzie et al., 1976; Heistad and Kontos, 1979; Baumbach and Heistad, 1985; Paulson et al., 1990). More so, should CPP falls below the lower boundary of CA, blood flow reduces and ischemia sets in (Hossmann, 2006).

The precise mechanism of CA is currently elusive; however, it is believed to be subject to the interaction of neurogenic, metabolic and myogenic factors (Czosnyka et al., 2009; Novak and Hajjar, 2010).

Intrinsic innervation is touted to be directly involved in the mechanisms of CA (Goadsby and Edvinsson, 2002) and extrinsic pathway is implausible, since CA is unimpaired following sympathetic and parasympathetic denervation in experimental animals (Busija and Heistad, 1984). The perikarya within the subcortical region of the brain, precisely those from the nucleus basalis, locus ceruleus and raphe nucleus project to cortical microvessels for the control of local blood flow by release of neurotransmitters (ACH, norepinephrine and 5HT) (Hamel, 2006). These released neurotransmitter substances interact with the receptors on smooth muscle, endothelium, or astrocytes to cause constriction or dilation, thus regulating blood supply according to the metabolic demand (Iadecola, 2004; Hamel, 2006; Drake and Iadecola, 2007).

Also, metabolic by-products released by the brain during CBF decrease are important for CA (Paulson, Strandgaar and Edvinsson, 1990). These substances, potassium, adenosine, and hydrogen ion triggers vasodilatation.

Another important component of the CA mechanism is the myogenic response of the cerebrovascular smooth muscle in regulating vascular tone. Constriction of the cerebral vasculature due to smooth muscle contraction ensues during pressure fluctuations at the upper boundary of the autoregulatory range of CPP, thus blood flow is not excessive (Fig. 1). Conversely, fluctuations at the lower limit of CPP is followed by vasodilatation (Fig.1) (Kontos, 1978,Busija and Heistad, 1984; Mellander, 1989; Osol et al., 2002).

Furthermore, the direct contact between astrocytes and the parenchymal arterioles of the brain have been shown to play a role in CA (Rennels and Nelson, 1975; Cohen, Molinatti and Hamel, 1997; Iadecola, 2004; Hamel, 2006; Drake and Iadecola, 2007; Zlokovic, 2008). Most microvessels at the subcortical level have astrocytic end-feet at the interface between them and neurons (Kulik et al., 2008), thus, under the direct influence of the vasoactive factors released by astrocytes (Murphy et al., 1994).

Interestingly, the type of cerebral vasculature may also contribute to CA in an unexpected manner, with respect to their response to blood flow changes. While basilar artery dilates in response to increased blood flow, MCA constricts Koller and Toth, (2012).

Under Anaesthesia

Anaesthesia puts the brain in a state of reduced neuronal activity, as a result CBF decreases in light of neurovascular coupling (Attwell et al., 2010). Also, in their studies in rats, Jones et al., (2002) reported that anaesthesia reduces the CCP levels below the lower limit of CA.

More importantly, anaesthetics have significant impact on CA as they affect the vasculature of the brain, directly or indirectly. Under the influence of volatile anaesthetics, calcium entry via voltage gated Ca2+ channels on vascular smooth muscle cells is reduced significantly, causing the vasculature to dilate (Bosnjak et al. 1992), thereby, directly overriding CA. Also, anaesthetics cause profound respiratory depression in spontaneously breathing animals, consequently PaCO2 increased.

Given that the vasculature of the brain is highly sensitive to changes in CO2, an increase value of PaCO2 stimulates cerebral vasodilatation (Kuschinsky, 1997; Willie et al., 2014); correspondingly CBF increases (Figure 2). These effects of anaesthetics lead ultimately to the failure of CA in mammals.

However, certain anaesthetics for example Ethomidate, preserves CA (Wang et al., 2010). This is mainly due to their ability to keep PaCO2 nearly constant within the nomal range without artificial ventilation (Lacombe et al. 2005; Joutel et al., 2010).

Fig. 2. Cerebral blood flow with respect to arterial pressure of CO2.

CBF increases as PaCO2 level increases beyond the level of 25 mmHg. However, at 80 mmHg blood vessels are maximally dilated and CBF remains constant with a further increase in PaCO2 values. Adapted from Adapted from Hill and Gwinnutt, no date.


During arterial occlusion, as in the case of ischaemic stroke, local cerebral perfusion pressure falls below the normal CA range while MAP does not change. With persistent occlusion, autoregulation fails (Reinhard et al., 2008; Reinhard et al., 2012; Immink et al., 2005; Atkins et al., 2010) and regional CBF further decreases. For this reason, blood pressure changes, high or low, results in poor outcome (Castillo et al, 2004; Aslanyan et al., 2003; Sandset et al., 2012). However, this is not entirely due to the failed autoregulatory capacity of the vessels during ischemia, but perhaps their normal vasodilatory capacity has reached a maximal limit (Petersen et al., 2015).

The impaired autoregulatory response following acute stroke has been observed both in the affected and contralateral hemispheres (Cupini et al., 2001; Dawson et al., 2000; Dawson, Panerai and Potter, 2003; Fieschi et al., 1988; Gelmers, 1982; Lisk et al., 1993; Hakim et al., 1989).


Aslanyan S, Fazekas F, Weir CJ, Horner S and Lees KR (2003). GAIN International Steering Committee and Investigators: Effect of blood pressure during the acute period of ischemic stroke on stroke outcome: a tertiary analysis of the GAIN International Trial. Stroke. 34: 2420–2425.

Atkins ER, Brodie FG, Rafelt SE, Panerai RB and Robinson TG (2010). Dynamic cerebral autoregulation is compromised acutely following mild ischaemic stroke but not transient ischaemic attack. Cerebrovasc. Dis. 29: 228–235.

Attwell D, Buchan AM, Charpak S et al. (2010). Glial and neuronal control of brain blood flow. Nature. 468: 232–43.

Baumbach GL and Heistad DD (1989). Remodeling of cerebral arterioles in chronic hypertension. Hypertension. 13: 968–972.

Betz E and Heuser D (1967). Cerebral cortical blood flow during changes of acid-base equilibrium the brain. J. Appl. Physiol. 23: 726-733.

Bosnjak ZJ, Aggarwal A, Turner LA, Kampine JM and Kampine JP (1992). Differential effects of halothane, enflurane, and isofluurane on Ca2 + transients and papillary muscle tension in guinea pigs. Anesthesiology. 76: 123–131

Buczek J, Karlin´ski M, Kobayashi A, BiaÅ‚ek P and CzÅ‚onkowska A (2013). Hyperperfusion syndrome after carotid endarterectomy and carotid stenting. Cerebrovasc. Dis. 35: 531–7.

Budohoski KP, Czosnyka M, Smielewski P, Kasprowicz M, Helmy A, Bulters D et al. (2012). Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke. 43: 3230–3237.

Busija DW and Heistad DD (1984). Factors involved in the physiological regulation of the cerebral circulation. Rev. Physiol. Biochem. Parmacol. 101: 161–211.

Castillo J, Leira R, García MM, Serena J, Blanco M and Dávalos A (2004). Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome. Stroke. 35: 520–526.

Cohen Z, Molinatti G and Hamel E (1997). Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J. Cereb. Blood Flow Metab. 17: 894–904.

Cotev S and Severinghaus JW (1969). Role of cerebrospinal fluid pH in management of respiratory problems. Anesth. Analg. 48: 42-47.

Cupini LM, Diomedi M, Placidi F, Silvestrini M and Giacomini P (2001). Cerebrovascular reactivity and subcortical infarctions. Arch. Neurol. 58: 577–581.

Czosnyka M, Brady K, Reinhard M, Smielewski P and Steiner LA (2009). Monitoring of cerebrovascular autoregulation: facts, myths, and missing links. Neurocritical Care. 10: 373–86.

Dawson SL, Blake MJ, Panerai RB and Potter JF (2000). Dynamic but not static cerebral autoregulation is impaired in acute ischaemic stroke. Cerebrovasc. Dis.10:126–132.

Dawson SL, Panerai RB and Potter JF (2003). Serial changes in static and dynamic cerebral autoregulation after acute ischaemic stroke. Cerebrovasc. Dis. 16:69–75.

Diedler J, Sykora M, Rupp A et al. (2009). Impaired cerebral vasomotor activity in spontaneous intracerebral hemorrhage. Stroke. 40: 815–9.

Drake CT and Iadecola C (2007). The role of neuronal signalling in controlling cerebral blood flow. Brain Lang. 102: 141–152.

Ekstrom-Jodal B, Haggendal E, Linder LE and Nilsson NJ (1971). Cerebral blood flow autoregulation at high arterial pressures and different levels of carbon dioxide tension in dogs. Eur. Neurol. 6:6-10.

Fieschi C, Argentino C, Toni D and Pozzilli C (1988). Calcium antagonists in ischemic stroke. J. Cardiovasc. Pharmacol. 12(6): 83–85.

Fisher JP, Ogoh S, Young CN, Raven PB and Fadel PJ (2008). Regulation of middle cerebral artery blood velocity during dynamic exercise in humans: influence of aging. J. Appl. Physiol. 105: 266–273.

Goadsby PJ and Edvinsson L (2002). Neurovascular control of the cerebral circulation, Lippincott Williams & Wilkins, Philadelphia, Pa, USA.

Gelmers HJ (1982). Effect of nimodipine (Bay e 9736) on postischaemic cerebrovascular reactivity, as revealed by measuring regional cerebral blood flow (rCBF). Acta Neurochir. (Wien). 63: 283–290.

Hakim AM, Evans AC, Berger L, Kuwabara H, Worsley K, Marchal G, Biel C, Pokrupa R, Diksic M and Meyer E (1989). The effect of nimodipine on the evolution of human cerebral infarction studied by PET. J. Cereb. Blood Flow Metab. 9: 523–534.

Hamel E (2006). Perivascular nerves and the regulation of cerebrovascular tone. J. Appl. Physiol. 100: 1059–1064.

Heistad DD and Kontos HA (1979). In: Handbook of Physiology: The Cardiovascular System III, Berne RM, Sperelakis N (Eds.). Bethesda, MD: American Physiological Society. 137–182.

Hossmann KA (2006). Pathophysiology and therapy of experimental stroke. Cell Mol. Neurobiol. 26: 1057-1083.

Iadecola C (2004). Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nature Reviews Neuroscience. 5(5): 347–360.

Immink RV, van Montfrans GA, Stam J, Karemaker JM, Diamant M and van Lieshout JJ (2005). Dynamic cerebral autoregulation in acute lacunar and middle cerebral artery territory ischemic stroke. Stroke. 36: 2595–2600.

Jones SC, Radinsky CR, Furlan AJ et al. (2002). Variability in the magnitude of the cerebral blood flow response and the shape of the cerebral blood flow pressure autoregulation curve during hypotension in normal rats [corrected]. Anesthesiology. 97: 488–96.

Joutel A, Monet-Lepretre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, Lemaire-Carrette B, Domenga V, Schedl A, Lacombe P and Hubner N (2010). Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J. Clin. Invest. 120: 433–445.

Koller A and Toth P (2012). Contribution of flow-dependent vasomotor mechanisms to the autoregulation of cerebral blood flow. J. Vasc. Res. 49: 375–389.

Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI and Patterson JL, Jr (1978). Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am. J. Physiol. 234: H371–H383.

Kulik T, Kusano Y, Aronhime S, Sandler AL and Winn HR (2008). Regulation of cerebral vasculature in normal and ischemic brain. Neuropharmacology. 55: 281–288.

Kuschinsky W (1997). Neuronal-vascular coupling. A unifying hypothesis. Adv. Exp. Med. Biol. 413: 167–176.

Lacombe P, Oligo C, Domenga V, Tournier-Lasserve E and Joutel A (2005). Impaired cerebral vasoreactivity in a transgenic mouse model of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy arteriopathy. Stroke. 36: 1053–1058.

Lassen NA (1959).Cerebral blood flow and oxygen consumption in man. Physiol. Rev. 39: 183–238.

Lassen NA (1974). Control of cerebral circulation in health and disease. Circ. Res. 34: 749–760.

Lisk DR, Grotta JC, Lamki LM, Tran HD, Taylor JW, Molony DA and Barron BJ (1993). Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography. Arch. Neurol. 50:855–862.

Liu J, Zhu YS, Hill C, Armstrong K, Tarumi T, Hodics T, Hynan LS and Zhang R (2013). Cerebral autoregulation of blood velocity and volumetric flow during steady-state changes in arterial pressure. Hypertension 62: 973– 979.

MacKenzie ET, Strandgaard S and Graham DI et al. (1976). Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Circ. Res. 39:33-41.

McHenry LC, Jr., West JW, Cooper ES, Goldberg HI and Jaffe ME (1974).Cerebral autoregulation in man. Stroke. 5: 695-706.

Mellander S (1989). Functional aspects of myogenic vascular control. J. Hypertens. 7(4): S21–S30.

Murphy S, Rich G, Orgren KI, Moore SA and Faraci FM (1994). Astrocyte-derived lipoxygenase product evokes endothelium-dependent relaxation of the basilar artery. J. Neurosci. Res. 38: 314–318.

Novak V and Hajjar I (2010). The relationship between blood pressure and cognitive function. Nature Reviews Cardiology. 7: 686–98.

Osol G, Brekke JF, McElroy-Yaggy K and Gokina NI (2002). Myogenic tone, reactivity, and forced dilatation: a three-phase model of in vitro arterial myogenic behavior. Am. J. Physiol. Heart Circ. Physiol. 283: H2260– H2267.

Oudegeest-Sander MH, van Beek AH, Abbink K, Olde Rikkert MG, Hopman MT and Claassen JA (2014). Assessment of dynamic cerebral autoregulation and cerebrovascular CO2 reactivity in ageing by measurements of cerebral blood flow and cortical oxygenation. Exp Physiol. 99: 586–598.

Panerai RB (1998). Assessment of cerebral pressure autoregulation in humans—a review of measurement methods. Physiol. Meas. 19: 305–338.

Paulson OB, Strandgaard S and Edvinsson L (1990). Cerebral autoregulation. Cerebrovasc. Brain Metab. Rev. 2: 161-192.

Petersen NH, Ortega-Gutierrez S, Reccius A, Masurkar A, Huang A and Marshall RS (2015). Dynamic Cerebral Autoregulation Is Transiently Impaired for One Week after Large-Vessel Acute Ischemic Stroke. Cerebrovasc. Dis. 39: 144–150.

Pires PW, Dams Ramos CM, Matin N and Dorrance AM (2013). The effects of hypertension on the cerebral circulation. Am. J. Physiol. Heart. Circ. Physiol. 304: 1598–1614,

Raichle ME and Stone HL (1971). Cerebral blood flow autoregulation and graded hypercapnia. Eur. Neurol. 6: 1-5.

Reinhard M, Wihler C, Roth M, Harloff A, Niesen WD, Timmer J et al. (2008). Cerebral autoregulation dynamics in acute ischemic stroke after rtPA thrombolysis. Cerebrovasc. Dis. 26: 147–155.

Reinhard M, Rutsch S, Lambeck J, Wihler C, Czosnyka M, Weiller C et al. (2012). Dynamic cerebral autoregulation associates with infarct size and outcome after ischemic stroke. Acta Neurol. Scand.125: 156–162. 

Rennels M and Nelson E (1975). Capillary innervation in the mammalian central nervous system: an electron microscope demonstration (1). Am. J. Anat. 144: 233–241.

Saeed NP, Panerai RB and Robinson TG (2013). The carotid artery as an alternative site to the middle cerebral artery for reproducible estimates of autoregulation index. Ultrasound Med. Biol. 39: 735–741.

Sandset EC, Murray GD, Bath PM, Kjeldsen SE and Berge E (2012). Scandinavian Candesartan Acute Stroke Trial (SCAST) Study Group: Relation between change in blood pressure in acute stroke and risk of early adverse events and poor outcome. Stroke. 43: 2108–2114.

Serrador JM, Sorond FA, Vyas M, Gagnon M, Iloputaife ID and Lipsitz LA (2005). Cerebral pressure-flow relations in hypertensive elderly humans: transfer gain in different frequency domains. J. Appl. Physiol. 98: 151–159.

Strandgaard S (1976). Autoregulation of cerebral blood flow in hypertensive patients. The modifying influence of prolonged antihypertensive treatment on the tolerance to acute, drug-induced hypotension. Circulation. 53: 720-727

Tiecks FP, Lam AM, Aaslid R and Newell DW (1995). Comparison of static and dynamic Cerebral autoregulation measurements. Stroke. 26: 1014–1019.

Wang Z, Schuler B, Vogel O, Arras M and Vogel J (2010). What is the optimal anesthetic protocol for measurements of cerebral autoregulation in spontaneously breathing mice? Exp. Brain Res. 207: 249–258.

Willie CK, Tzeng YC, Fisher JA and Ainslie PN (2014). Integrative regulation of human brain blood flow. J. Physiol. 592: 841–859.

Zhang R, Witkowski S, Fu Q, Claassen JA and Levine BD (2007). Cerebral hemodynamics after short- and long-term reduction in blood pressure in mild and moderate hypertension. Hypertension. 49: 1149–1155.

Zlokovic BV (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 57: 178–201.

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