Ауторегуляция мозгового кровотока в норме и при патологии

Метаболические потребности головного мозга (ГМ) в значительной степени зависят от интенсивности функционирования различных его отделов, что требует постоянной регуляции уровня местного кровотока. Важность точной и своевременной регуляции мозгового кровотока усиливается отсутствием запасов субстратов для автономного получения энергии в нервной ткани. При этом состояние системной гемодинамики может оказывать значительное влияние на органный кровоток. В то же время, учитывая роль центральной нервной системы в обеспечении всех физиологических процессов, регуляция органного мозгового кровотока направлена на минимизацию возможных неблагоприятных последствий влияния нарушений системной гемодинамики. В связи с этим регуляция мозгового кровотока основана на множественных и сложных физиологических механизмах, реализующихся на различных уровнях. Базовым уровнем регуляции мозгового кровотока является миогенная реакция, которая обеспечивает феномен ауторегуляции кровотока в ГМ. В настоящем обзоре будут рассмотрены физиологические механизмы, лежащие в основе миогенной регуляции, а также изменение этой регуляции при различных заболеваниях

1. Bayliss N. On the local reactions of the arterial wall to changes of internal pressure. J Physiol. 1902; 28:220–231. DOI: 10.1113/jphysiol.1902.sp000911.

2. Антонов В.И., Семенютин В.Б., Алиев В.А. Модели и методы исследования ауторегуляции мозгового кровообращения человека. Научно-технические ведомости Санкт-Петербургского государственного политехнического университета. Физико-математические науки. 2020; 13(3): 136–155. DOI: 10.18721/JPM.13311.

3. Kontos HA, Wei EP, Raper AJ et al. Role of tissue hypoxia in local regulation of cerebral microcirculation. Am J Physiol. 1978; 234: H582–H591. DOI 10.1152/ajpheart.1978.234.5.H582

4. Mellander S. Functional aspects of myogenic vascular control. J Hypertens Suppl. 1989 Sep;7(4):S21-30;

5. Busija DW, Heistad DD. Factors involved in the physiological regulation of the cerebral circulation. Rev Physiol Biochem Pharmacol. 1984;101:161-211. doi: 10.1007/BFb0027696.

6. Carlström M, Wilcox CS, Arendshorst WJ. Renal autoregulation in health and disease. Physiol Rev. 2015;95(2):405-511. doi: 10.1152/physrev.00042.2012.

7. Osol G, Brekke JF, McElroy-Yaggy K, Gokina NI. Myogenic tone, reactivity, and forced dilatation: a three-phase model of in vitro arterial myogenic behavior. Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2260-7. doi: 10.1152/ajpheart.00634.2002. Epub 2002 Aug 22.

8. Hill-Eubanks DC, Gonzales AL, Sonkusare SK, Nelson MT. Vascular TRP channels: performing under pressure and going with the flow. Physiology (Bethesda). 2014;29(5):343-60. doi: 10.1152/physiol.00009.2014.

9. Drummond HA, Grifoni SC, Jernigan NL. A new trick for an old dogma: ENaC proteins as mechanotransducers in vascular smooth muscle. Physiology (Bethesda). 2008; 23:23-31. doi: 10.1152/physiol.00034.2007.

10. Schubert R, Lidington D, Bolz SS. The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction. Cardiovasc Res. 2008; 77(1):8-18. doi: 10.1016/j.cardiores.2007.07.018. PMID: 17764667.

11. Moosmang S, Schulla V, Welling A, Feil R, Feil S, Wegener JW, Hofmann F, Klugbauer N. Dominant role of smooth muscle L-type calcium channel Cav1.2 for blood pressure regulation. EMBO J. 2003; 17;22(22):6027-34. doi: 10.1093/emboj/cdg583.

12. Cipolla MJ, Gokina NI, Osol G. Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior. FASEB J. 2002;16(1):72-6. doi: 10.1096/cj.01-0104hyp.

13. Coulson RJ, Cipolla MJ, Vitullo L, Chesler NC. Mechanical properties of rat middle cerebral arteries with and without myogenic tone. J Biomech Eng. 2004; 126(1): 76-81. doi: 10.1115/1.1645525.

14. Lagaud G, Gaudreault N, Moore ED, Van Breemen C, Laher I. Pressure-dependent myogenic constriction of cerebral arteries occurs independently of voltage-dependent activation. Am J Physiol Heart Circ Physiol. 2002;283(6):H2187-95. doi: 10.1152/ajpheart.00554.2002.

15. Osol G, Laher I, Cipolla M. Protein kinase C modulates basal myogenic tone in resistance arteries from the cerebral circulation. Circ Res. 1991; 68(2):359-67. doi: 10.1161/01.res.68.2.359.

16. Jaggar JH. Intravascular pressure regulates local and global Ca(2+) signaling in cerebral artery smooth muscle cells. Am J Physiol Cell Physiol. 2001; 281(2):C439-48. doi: 10.1152/ajpcell.2001.281.2.C439.

17. Jaggar JH, Porter VA, Lederer WJ, Nelson MT. Calcium sparks in smooth muscle. Am J Physiol Cell Physiol. 2000; 278(2):C235-56. doi: 10.1152/ajpcell.2000.278.2.C235.

18. Cipolla MJ, Osol G. Vascular smooth muscle actin cytoskeleton in cerebral artery forced dilatation. Stroke. 1998; 29(6):1223-8. doi: 10.1161/01.str.29.6.1223.

19. Paternò R, Heistad DD, Faraci FM. Potassium channels modulate cerebral autoregulation during acute hypertension. Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H2003-7. doi: 10.1152/ajpheart.2000.278.6.H2003.

20. Hamner JW, Tan CO. Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation. Stroke. 2014; 45(6):1771-7. doi: 10.1161/STROKEAHA.114.005293.

21. Saleem S, Teal PD, Howe CA, Tymko MM, Ainslie PN, Tzeng YC. Is the Cushing mechanism a dynamic blood pressure-stabilizing system? Insights from Granger causality analysis of spontaneous blood pressure and cerebral blood flow. Am J Physiol Regul Integr Comp Physiol. 2018; 315(3):R484-R495. doi: 10.1152/ajpregu.00032.2018.

22. Kimmerly DS, Tutungi E, Wilson TD, Serrador JM, Gelb AW, Hughson RL et al. Circulating norepinephrine and cerebrovascular control in conscious humans. Clin Physiol Funct Imaging. 2003; 23(6):314-9. doi: 10.1046/j.1475-0961.2003.00507.x.

23. Tzeng YC, Lucas SJ, Atkinson G, Willie CK, Ainslie PN. Fundamental relationships between arterial baroreflex sensitivity and dynamic cerebral autoregulation in humans. J Appl Physiol (1985). 2010 May;108(5):1162-8. doi: 10.1152/japplphysiol.01390.2009.

24. Xing CY, Tarumi T, Meijers RL, Turner M, Repshas J, Xiong L, Ding K, Vongpatanasin W, Yuan LJ, Zhang R. Arterial Pressure, Heart Rate, and Cerebral Hemodynamics Across the Adult Life Span. Hypertension. 2017 Apr;69(4):712-720. doi: 10.1161/HYPERTENSIONAHA.116.08986.

25. Claassen JAHR, Thijssen DHJ, Panerai RB, Faraci FM. Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation. Physiol Rev. 2021; 101(4):1487-1559. doi: 10.1152/physrev.00022.2020.

26. Lassen NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959; 39(2):183-238. doi: 10.1152/physrev.1959.39.2.183.

27. Brassard P, Labrecque L, Smirl JD, Tymko MM, Caldwell HG, Hoiland RL et al. Losing the dogmatic view of cerebral autoregulation. Physiol Rep. 2021; 9(15):e14982. doi: 10.14814/phy2.14982.

28. Brassard P, Tymko MM, Ainslie PN. Sympathetic control of the brain circulation: Appreciating the complexities to better understand the controversy. Auton Neurosci. 2017; 207:37-47. doi: 10.1016/j.autneu.2017.05.003.

29. Panerai RB, Barnes SC, Nath M, Ball N, Robinson TG, Haunton VJ. Directional sensitivity of dynamic cerebral autoregulation in squat-stand maneuvers. Am J Physiol Regul Integr Comp Physiol. 2018; 315(4):R730-R740. doi: 10.1152/ajpregu.00010.2018.

30. Hossmann KA. Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol. 2006; 26(7-8):1057-83. doi: 10.1007/s10571-006-9008-1.

31. Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron. 2010 Jul 29;67(2):181-98. doi: 10.1016/j.neuron.2010.07.002. Erratum in: Neuron. 2010; 68(1):161.

32. Phillips SJ, Whisnant JP. Hypertension and the brain. The National High Blood Pressure Education Program. Arch Intern Med. 1992; 152(5):938-45.

33. Euser AG, Cipolla MJ. Cerebral blood flow autoregulation and edema formation during pregnancy in anesthetized rats. Hypertension. 2007; 49(2):334-40. doi: 10.1161/01.HYP.0000255791.54655.29.

34. Masamoto K., Tanishita K. Oxygen transport in brain tissue // J Biomech Eng. – 2009. – V. 131. – P. 74–82.

35. Steiner L.A., Gupta A.K., Menon D.K. Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity // Br J Anaesth. – 2003. – V. 90. – P. 774–786.

36. Hoiland R.L., Bain A.R., Rieger M.G. et al. Hypoxemia, oxygen content, and the regulation of cerebral blood flow // Am J Physiol Regul Integr Comp Physiol. – 2016. – V. 310. – P. R398–R413.

37. Taguchi H., Heistad D.D., Kitazono T. et al. ATP-sensitive K+ channels mediate dilatation of cerebral arterioles during hypoxia // Circ Res.– 1994. – V. 74. – P. 1005–1008.

38. Phillis J.W. Adenosine and adenine nucleotides as regulators of cerebral blood flow: roles of acidosis, cell swelling, and KATP channels // Crit Rev Neurobiol. – 2004. – V. 16. – P. 237–270.

39. Xu K., Lamanna J.C. Chronic hypoxia and the cerebral circulation // J Appl Physiol. – 2006. –V. 100. – P. 725–730

40. van Wijnen VK, Ten Hove D, Gans ROB, Nieuwland W, van Roon AM, Ter Maaten JC, Harms MPM. Orthostatic blood pressure recovery patterns in suspected syncope in the emergency department. Emerg Med J. 2018 Apr;35(4):226-230. doi: 10.1136/emermed-2017-207207.

41. Slupe AM, Kirsch JR. Effects of anesthesia on cerebral blood flow, metabolism, and neuroprotection. J Cereb Blood Flow Metab. 2018 Dec;38(12):2192-2208. doi: 10.1177/0271678X18789273

42. Matta BF, Heath KJ, Tipping K, Summors AC. Direct cerebral vasodilatory effects of sevoflurane and isoflurane. Anesthesiology. 1999 Sep;91(3):677-80. doi: 10.1097/00000542-199909000-00019

43. Braz ID, Flück D, Lip GYH, Lundby C, Fisher JP. Impact of aerobic fitness on cerebral blood flow and cerebral vascular responsiveness to CO2 in young and older men. Scand J Med Sci Sports. 2017 Jun;27(6):634-642. doi: 10.1111/sms.12674.

44. Quistorff B, Secher NH, Van Lieshout JJ. Lactate fuels the human brain during exercise. FASEB J. 2008 Oct;22(10):3443-9. doi: 10.1096/fj.08-106104.

45. Strandgaard S, Paulson OB. Regulation of cerebral blood flow in health and disease. J Cardiovasc Pharmacol. 1992;19 Suppl 6:S89-93. doi: 10.1097/00005344-199219006-00014.

46. Shekhar S, Liu R, Travis OK, Roman RJ, Fan F. Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review. J Pharm Sci Exp Pharmacol. 2017;2017(1):21-27.

47. Troisi E, Attanasio A, Matteis M, Bragoni M, Monaldo BC, Caltagirone C et al. Cerebral hemodynamics in young hypertensive subjects and effects of atenolol treatment. J Neurol Sci. 1998;159(1): 115–119. doi:10.1016/s0022-510x(98)00147-6.

48. Serrador JM, Sorond FA, Vyas M, Gagnon M, Iloputaife ID, Lipsitz LA. Cerebral pressure-flow relations in hypertensive elderly humans: transfer gain in different frequency domains. J Appl Physiol (1985). 2005 Jan;98(1):151-9. doi: 10.1152/japplphysiol.00471.2004.

49. Ding J, Davis-Plourde KL, Sedaghat S, Tully PJ, Wang W, Phillips C et al. Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies. Lancet Neurol. 2020; 19(1):61-70. doi: 10.1016/S1474-4422(19)30393-X.

50. Claassen JA, Levine BD, Zhang R. Dynamic cerebral autoregulation during repeated squat-stand maneuvers. J Appl Physiol. 2009; 106(1):153-60. doi: 10.1152/japplphysiol.90822.2008.

51. van Beek AH, Lagro J, Olde-Rikkert MG, Zhang R, Claassen JA. Oscillations in cerebral blood flow and cortical oxygenation in Alzheimer's disease. Neurobiol Aging. 2012; 33(2):428.e21-31. doi: 10.1016/j.neurobiolaging.2010.11.016.

52. Nasr N, Czosnyka M, Arevalo F, Hanaire H, Guidolin B, Larrue V. Autonomic neuropathy is associated with impairment of dynamic cerebral autoregulation in type 1 diabetes. Auton Neurosci. 2011 Feb 24;160(1-2):59-63. doi: 10.1016/j.autneu.2010.10.001

53. Vianna LC, Deo SH, Jensen AK, Holwerda SW, Zimmerman MC, Fadel PJ. Impaired dynamic cerebral autoregulation at rest and during isometric exercise in type 2 diabetes patients. Am J Physiol Heart Circ Physiol. 2015 Apr 1;308(7):H681-7. doi: 10.1152/ajpheart.00343.2014

54. Markus HS. Cerebral perfusion and stroke. J Neurol Neurosurg Psychiatry. 2004; 75(3):353-61. doi: 10.1136/jnnp.2003.025825.

55. Liebeskind DS. Collaterals in acute stroke: beyond the clot. Neuroimaging Clin N Am. 2005; 15(3):553-73, x. doi: 10.1016/j.nic.2005.08.012.

56. Yang M, Yang Z, Yuan T, Feng W, Wang P. A Systemic Review of Functional Near-Infrared Spectroscopy for Stroke: Current Application and Future Directions. Front Neurol. 2019; 10:58. doi: 10.3389/fneur.2019.00058.

57. Lam MY, Haunton VJ, Robinson TG, Panerai RB. 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(3):H673-H683. doi: 10.1152/ajpheart.00550.2018.

58. Saeed NP, Panerai RB, Horsfield MA, Robinson TG. Does stroke subtype and measurement technique influence estimation of cerebral autoregulation in acute ischaemic stroke? Cerebrovasc Dis. 2013; 35(3):257-61. doi: 10.1159/000347075.

59. Intharakham K, Beishon L, Panerai RB, Haunton VJ, Robinson TG. Assessment of cerebral autoregulation in stroke: A systematic review and meta-analysis of studies at rest. J Cereb Blood Flow Metab. 2019; 39(11):2105-2116. doi: 10.1177/0271678X19871013.

60. Guo ZN, Liu J, Xing Y, Yan S, Lv C, Jin H, Yang Y. Dynamic cerebral autoregulation is heterogeneous in different subtypes of acute ischemic stroke. PLoS One. 2014; 9(3):e93213. doi: 10.1371/journal.pone.0093213.

61. Tutaj M, Miller M, Krakowska-Stasiak M, Piątek A, Hebda J, Lątka Met al. Dynamic cerebral autoregulation is compromised in ischaemic stroke of undetermined aetiology only in the non-affected hemisphere. Neurol Neurochir Pol. 2014; 48(2):91-7. doi: 10.1016/j.pjnns.2013.12.006.

62. Reinhard M, Rutsch S, Lambeck J, Wihler C, Czosnyka M, Weiller C et al. Dynamic cerebral autoregulation associates with infarct size and outcome after ischemic stroke. Acta Neurol Scand. 2012; 125(3):156-62. doi: 10.1111/j.1600-0404.2011.01515.x.

63. Guo ZN, Xing Y, Wang S, Ma H, Liu J, Yang Y. Characteristics of dynamic cerebral autoregulation in cerebral small vessel disease: Diffuse and sustained. Sci Rep. 2015; 5:15269. doi: 10.1038/srep15269.

64. Castro P, Azevedo E, Sorond F. Cerebral Autoregulation in Stroke. Curr Atheroscler Rep. 2018; 20(8):37. doi: 10.1007/s11883-018-0739-5.

65. Ito T, Yamakawa H, Bregonzio C, Terrón JA, Falcón-Neri A, Saavedra JM. Protection against ischemia and improvement of cerebral blood flow in genetically hypertensive rats by chronic pretreatment with an angiotensin II AT1 antagonist. Stroke. 2002; 33(9):2297-303. doi: 10.1161/01.str.0000027274.03779.f3.

66. Tian G, Ji Z, Huang K, Lin Z, Pan S, Wu Y. Dynamic cerebral autoregulation is an independent outcome predictor of acute ischemic stroke after endovascular therapy. BMC Neurol. 2020; 20(1):189. doi: 10.1186/s12883-020-01737-w.

67. Beishon L, Minhas JS, Nogueira R, Castro P, Budgeon C, Aries M et al. INFOMATAS multi-center systematic review and meta-analysis individual patient data of dynamic cerebral autoregulation in ischemic stroke. Int J Stroke. 2020; 15(7):807-812. doi: 10.1177/1747493020907003.