Modern aspects of the relationship between the functional state of the autonomic nervous system and clinical and laboratory indices of the bodyʼs homeostasis in brain injuries

A.V. Grechko, Yu.Yu. Kiryachkov, M.V. Petrova

Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow

For correspondence: Yuri Yu. Kiryachkov — MD, head of the department of surgical and anesthesia-resuscitation technologies Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology; e-mail: kirychyu@yandex.ru

For citation: Grechko AV, Kiryachkov YuYu, Petrova MV. Modern aspects of the relationship between the functional state of the autonomic nervous system and clinical and laboratory indices of the bodyʼs homeostasis in brain injuries. Alexander Saltanov Intensive Care Herald. 2018;2:79–86.

DOI: 10.21320/1818-474X-2018-2-79-86


A review of the literature is devoted to the analysis of the role of the autonomic nervous system as the main regulator of the bodyʼs homeostasis in heterotopic (anoxia, craniocerebral trauma, cerebral circulation disorder) brain damage. First of all, clinical, pathophysiological definitions and methods of pharmacological correction of manifestations of sympathetic and parasympathetic hyperactivity (paroxysmal sympathetic hyperactivity — PSH, paroxysmal parasympathetic hyperactivity — PPH) are considered first. An important aspect of the review is the evaluation of publications devoted to the prevention and therapy of systemic inflammatory response and secondary neuroinflammation based on functional adaptive responses of the autonomic nervous system. The mechanisms of the so-called cholinergic anti-inflammatory pathway to systemic and local inflammatory reactions are discussed. The aspects of the influence of the norm and pathology of the autonomic nervous system on the metabolism and energy balance of the organism are described in detail. The prospects of normalizing the nutritional status through therapeutic effects on the structures of the autonomic nervous system located in the hypothalamic zones of the brain, changes in the regulatory influences of parasympathetic and sympathetic nerves, the innervating liver, intestine, and pancreas are estimated. The interactions of peripheral structures of the autonomic nervous system and microbiota are considered separately. The relationship is shown in detail and possible mechanisms of the functional status of the sympathetic or parasympathetic nervous system in muscular dystonia, respiratory insufficiency and veining are discussed from the point of view of evaluation and correction of the most important constant of autonomic instability in the form of peripheral chemoreceptor insufficiency.

Keywords: sympathetic and parasympathetic hyperactivity; regulation of energy homeostasis, cholinergic anti-inflammatory pathway, chemoreceptor sensitivity

Received: 22.05.2018


References

  1. Osteraas N.D., Lee V.H. Neurocardiology. Handb. Clin. Neurol. 2017; 140: 49–65.
  2. Mirow S., Wilson S.H., Weaver L.K.,et al. Linear analysis of heart rate variability in post-concussive syndrome. Undersea Hyperb. Med. 2016; 43(5): 531–547.
  3. Laranjo S., Geraldes V., Oliveira M.,et al. Insights into the background of autonomic medicine. Rev. Port. Cardiol. 2017; 36(10): 757–771.
  4. Pozzi M., Locatelli F., Galbiati S.,et al. Re: “Paroxysmal Sympathetic Hyperactivity: A New Era for Diagnosis and Treatment”. J. Head Trauma Rehabil. 2015; 30(5): 366–367.
  5. Barha C.K., Nagamatsu L.S. Basics of neuroanatomy and neurophysiology. Handb. Clin. Neurol. 2016; 138: 53–68.
  6. Abou E. Fadl M.H., O’Phelan K.H. Management of traumatic brain injury: An Update. Neurol. Clin. 2017; 35(4): 641–653.
  7. Godoy D.A., Panhke P., Guerrero Suarez P.D.,et al. Paroxysmal sympathetic hyperactivity: An entity to keep in mind. Med. Intensiva. 2017: pii: S0210-5691(17)30308-X.
  8. Letzkus L., Keim-Malpass J., Kennedy C. Paroxysmal sympathetic hyperactivity: Autonomic instability and muscle over-activity following severe brain injury. Brain Inj. 2016; 30(10): 1181–1185.
  9. Shukla D. Over-diagnosis of paroxysmal sympathetic hyperactivity. Neurol. India. 2017; 65(3): 683.
  10. Martin-Gallego A., Andrade-Andrade I., Dawid-Milner M.S.,et al. Autonomic dysfunction elicited by a medulla oblongata injury after fourth ventricle tumor surgery in a pediatric patient. Auton. Neurosci. 2016; 194: 52–57.
  11. Kern J., Bodek D., Niazi O.T., Maher J. Refractory Case of Paroxysmal Autonomic Instability With Dystonia Syndrome Secondary to Hypoxia. Chest. 2016; 149(2): e39–40.
  12. Ofte H.K., Hanno T., Alstadhaug K.B. Reduced cranial parasympathetic tone during the remission phase of cluster headache. Cephalalgia. 2015; 35(6): 469–477.
  13. Baguley I.J., Perkes I.E., Fernandez-Ortega J.F.,et al. Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on conceptual definition, nomenclature, and diagnostic criteria. J. Neurotrauma. 2014; 31(17): 1515–1520.
  14. Meier K., Lee K. Neurogenic Fever. J. Intensive Care Med. 2017; 32(2): 124–129.
  15. Raithel D.S., Ohler K.H., Porto I.,et al. Morphine: An Effective Abortive Therapy for Pediatric Paroxysmal Sympathetic Hyperactivity After Hypoxic Brain Injury. J. Pediatr. Pharmacol. Ther. 2015; 20(4): 335–340.
  16. Godo S., Irino S., Nakagawa A.,et al. Diagnosis and Management of Patients with Paroxysmal Sympathetic Hyperactivity following Acute Brain Injuries Using a Consensus-Based Diagnostic Tool: A Single Institutional Case Series. Tohoku J. Exp. Med. 2017; 243(1): 11–18.
  17. Meyfroidt G., Baguley I.J., Menon D.K. Paroxysmal sympathetic hyperactivity: the storm after acute brain injury. Lancet Neurol. 2017; 16(9): 721–729.
  18. Termsarasab P., Frucht S.J. Dystonic storm: a practical clinical and video review. J. Clin. Mov. Disord. 2017; 4: 10.
  19. Vistisen S.T., Hansen T.K., Jensen J.,et al. Heart rate variability in neurorehabilitation patients with severe acquired brain injury. Brain Inj. 2014; 28(2): 196–202.
  20. Berger M.J., Kimpinski K., Currie K.D.,et al. Multi-Domain Assessment of Autonomic Function in Spinal Cord Injury Using a Modified Autonomic Reflex Screen. J. Neurotrauma. 2017; 34(18): 2624–2633.
  21. Malik M., Huikuri H., Lombardi F.,et al. The purpose of heart rate variability measurements. Clin. Auton. Res. 2017; 27(3): 139–140.
  22. Manogue M., Hirsh D.S., Lloyd M. Cardiac electrophysiology of patients with spinal cord injury. Heart Rhythm. 2017; 14(6): 920–927.
  23. Vähätalo L.H., Ruohonen S.T., Mäkelä S.,et al. Neuropeptide Y in the noradrenergic neurones induces obesity and inhibits sympathetic tone in mice. Acta Physiol. (Oxf). 2015; 213(4): 902–919.
  24. Hoarau X., Richer E., Dehail P., Cuny E. Comparison of long-term outcomes of patients with severe traumatic or hypoxic brain injuries treated with intrathecal baclofen therapy for dysautonomia. Brain Inj. 2012; 26(12): 1451–1463.
  25. Fernandez-Ortega J.F., Prieto-Palomino M.A., Garcia-Caballero M.,et al. Paroxysmal sympathetic hyperactivity after traumatic brain injury: clinical and prognostic implications. J. Neurotrauma. 2012; 29(7): 1364–1370.
  26. Bartolo M., Bargellesi S., Castioni C.A.,et al. Mobilization in early rehabilitation in intensive care unit patients with severe acquired brain injury: An observational study. J. Rehabil. Med. 2017; 49(9): 715–722.
  27. Riganello F., Cortese M.D., Arcuri F.,et al. Autonomic Nervous System and Outcome after Neuro-Rehabilitation in Disorders of Consciousness. J. Neurotrauma. 2016; 33(4): 423–424.
  28. Esterov D., Greenwald B.D. Autonomic dysfunction after mild traumatic brain injury. Brain Sci. 2017; 7(8): pii: E100.
  29. Hilz M.J., Wang R., Markus J.,et al. Severity of traumatic brain injury correlates with long-term cardiovascular autonomic dysfunction. J. Neurol. 2017; 264(9): 1956–1967.
  30. Hinson H.E., Schreiber M.A., Laurie A.L.,et al. Early fever as a predictor of paroxysmal sympathetic hyperactivity in traumatic brain injury. J. Head Trauma Rehabil. 2017; 32(5): E50–E54.
  31. Mathew M., Deepika A., Shukla D.,et al. Paroxysmal sympathetic hyperactivity in severe traumatic brain injury. Acta Neurochir (Wien). 2016; 158(11): 2047–2052.
  32. Formisano R., Contrada M., Aloisi M.,et al. Improvement rate of patients with severe brain injury during post-acute intensive rehabilitation. Neurol. Sci. 2018; 39(4): 753–755.
  33. Sykora M., Czosnyka M., Liu X., et al. Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study. Crit. Care Med. 2016; 44(6): 1173–1181.
  34. Rincon F.,Hunter K., Schorr C., et al. The epidemiology of spontaneous fever and hypothermia on admission of brain injury patients to intensive care units: a multicenter cohort study. J. Neurosurg. 2014; 121(4): 950–960.
  35. Feng Y.,Zheng X., Fang Z. Treatment Progress of Paroxysmal Sympathetic Hyperactivity after Acquired Brain Injury. Pediatr. Neurosurg. 2015; 50(6): 301–309.
  36. Samuel S., Allison T.A., Lee K., Choi H.A. Pharmacologic management of paroxysmal sympathetic hyperactivity after brain injury. J. Neurosci. Nurs. 2016; 48(2): 82–89.
  37. May C.C., Oyler D.R., Parli S.E., Talley C.L. Rectal propranolol controls paroxysmal sympathetic hyperactivity: a case report. Pharmacotherapy. 2015; 35(4): e27–31.
  38. Allen N.M., Lin J.P., Lynch T., King M.D. Status dystonicus: a practice guide. Dev. Med. Child Neurol. 2014; 56(2): 105–112.
  39. Peng Y., Haifeng Z., Haodong C.,et al. Dexmedetomidine attenuates acute paroxysmal sympathetic hyperactivity. Oncotarget. 2017; 8(40): 69012–69019.
  40. Jiang L., Hu M., Lu Y.,et al. The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis. J. Clin. Anesth. 2017; 40: 25–32.
  41. Chen Y., Zhang X., Zhang B.,et al. Dexmedetomidine reduces the neuronal apoptosis related to cardiopulmonary bypass by inhibiting activation of the JAK2-STAT3 pathway. Drug Des. Devel. Ther. 2017; 11:2787–2799.
  42. Xu K.L., Liu X.Q., Yao Y.L.,et al. Effect of dexmedetomidine on rats with convulsive status epilepticus and association with activation of cholinergic anti-inflammatory pathway. Biochem. Biophys Res. Commun. 2018; 495(1): 421–426.
  43. Yamanaka D., Kawano T., Nishigaki A.,et al. Preventive effects of dexmedetomidine on the development of cognitive dysfunction following systemic inflammation in aged rats. J. Anesth. 2017; 31(1): 25–35.
  44. Hu J., Vacas S., Feng X.,et al. Dexmedetomidine Prevents Cognitive Decline by Enhancing Resolution of High Mobility Group Box 1 Protein-induced Inflammation through a Vagomimetic Action in Mice. Anesthesiology. 2018; 128(5): 921–931.
  45. Carod-Artal F.J. Infectious diseases causing autonomic dysfunction. Clin. Auton. Res. 2018; 28(1): 67–81.
  46. Godbolt A.K., Stenberg M., Jakobsson J.,et al. Complications during recovery from severe traumatic brain injury: frequency and associations with outcome. BMJ Open. 2015; 5(4): e007208.
  47. Quek A.M., Britton J.W., McKeon A.,et al. Autoimmunne epilepsy: clinical characteristics and response to immunotherapy. Arch. Neurol. 2012; 69(5): 582–593.
  48. Bauer J., Becker A.J., Elyaman W.,et al. Innate and adaptive immunity in human epilepsies. Epilepsia. 2017; 58(Suppl. 3): 57–68.
  49. Gaddam S.S.,Buell T., Robertson C.S. Systemic manifestations of traumatic brain injury. Handb. Clin. Neurol. 2015; 127: 205–218.
  50. Shin S.S., Dixon C.E. Alterations in Cholinergic Pathways and Therapeutic Strategies Targeting Cholinergic System after Traumatic Brain Injury. J. Neurotrauma. 2015; 32(19): 1429–1440.
  51. Lu J., Goh S.J., Tng P.Y.,et al. Systemic inflammatory response following acute traumatic brain injury. Front. Biosci. (Landmark Ed). 2009; 14: 3795–3813.
  52. Toklu H.Z., Tümer N. Oxidative Stress, Brain Edema, Blood–Brain Barrier Permeability, and Autonomic Dysfunction from Traumatic Brain Injury. In: Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015.
  53. Dash P.K., Zhao J., Kobori N.,et al. Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood-Brain Barrier Permeability following Experimental Traumatic Brain Injury. J. Neurosci. 2016; 36(9): 2809–2818.
  54. Frasch M.G., Szynkaruk M., Prout A.P.,et al. Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway? J. Neuroinflammation. 2016; 13(1): 103.
  55. Nicholls A.J., Wen S.W., Hall P.,et al. Activation of the sympathetic nervous system modulates neutrophil function. J. Leukoc. Biol. 2018; 103(2): 295–309.
  56. Han C., Rice M.W., Cai D. Neuroinflammatory and autonomic mechanisms in diabetes and hypertension. Am. J. Physiol. Endocrinol. Metab. 2016; 311(1): 32–41.
  57. Hung C.Y., Tseng S.H., Chen S.C.,et al. Cardiac autonomic status is associate with spasticity in post-stroke patients. Neuroreabilitation. 2014; 34(2): 227–233.
  58. Garrison M.K., Schmit B.D. Flexor reflex decreases during sympathetic stimulation in chronic human spinal cord injury. Exp. Neurol. 2009; 219(2): 507–515.
  59. Bickelhaupt B., Richard M., Trbovich M. Advanced Hip Osteoarthritis Causing Autonomic Dysreflexia and Severe Spasticity in a Patient With Spinal Cord Injury: PMR. 2017; 9(10): 1047–1050.
  60. Canon S., Shera A., Phan N.M.,et al. Autonomic dysreflexia during urodynamics in children and adolescents with spinal cord injury or severe neurologic disease. J. Pediatr. Urol. 2015; 11(1): 32.e1–4.
  61. Marina N., Turovsky E., Christie I.N.,et al. Brain metabolic sensing and metabolic signaling at the level of an astrocyte. Glia. 2017; 66(6): 1185–1199.
  62. Maldonado-Ruiz R., Fuentes-Mera L., Camacho A. Central Modulation of Neuroinflammation by Neuropeptides and Energy-Sensing Hormones during Obesity. Biomed. Res. Int. 2017; 2017: 7949582.
  63. Costa J., Moreira A., Moreira P.,et al. Effects of weight changes in the autonomic nervous system: A systematic review and meta-analysis. Clin. Nutr. 2018: pii: S0261-5614(18)30006-2.
  64. Wang Y.Y., Lin S.Y., Chuang Y.H.,et al. Endocrinology. Activation of hepatic inflammatory pathways by catecholamines is associated with hepatic insulin resistance in male ischemic stroke rats. 2014; 155(4): 1235–1246.
  65. Rothberg L.J., Lees T., Clifton-Bligh R., Lal S. Association Between Heart Rate Variability Measures and Blood Glucose Levels: Implication for Noninvasive Glucose Monitoring for Diabetes. Diabetes Technol. Ther. 2016; 18(6): 366–376.
  66. Croizier S., Prevot V., Bouret S.G. Leptin Controls Parasympathetic Wiring of the Pancreas during Embryonic Life. Cell Rep. 2016; 15(1): 36–44.
  67. Meyer M.L., Gotman N.M., Soliman E.Z.,et al. Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Cardiovasc. Diabetol. 2016; 15: 45.
  68. Yahagi N. Hepatic Control of Energy Metabolism via the Autonomic Nervous System. J. Atheroscler. Thromb. 2017; 24(1): 14–18.
  69. Flak J.N., Arble D., Pan W.,et al. A leptin-regulated circuit controls glucose mobilization during noxious stimuli. J. Clin. Invest. 2017; 127(8): 3103–3113.
  70. Hill J.W., Faulkner L.D. The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances. Neuroendocrinology. 2017; 104(4): 330–346.
  71. Gavini C.K., Jones W.C., Novak C.M. Ventromedial hypothalamic melanocortin receptor activation: regulation of activity energy expenditure and skeletal muscle thermogenesis. J. Physiol. 2016; 594(18): 5285–5301.
  72. Zhang Z., Boelen A., Bisschop P.H.,et al. Hypothalamic effects of thyroid hormone. Mol. Cell. Endocrinol. 2017; 458: 143–148.
  73. Gao H., Molinas A.J., Miyata K.,et al. Overactivity of Liver-Related Neurons in the Paraventricular Nucleus of the Hypothalamus: Electrophysiological Findings in db/db Mice. J. Neurosci. 2017; 37(46): 11140–11150.
  74. Isaacs D., Prasad-Reddy L., Srivastava S.B. Role of glucagon-like peptide 1 receptor agonists in management of obesity. Am. J. Health Syst. Pharm. 2016; 73(19): 1493–1507.
  75. Khound R., Taher J., Baker C.,et al. GLP-1 Elicits an Intrinsic Gut-Liver Metabolic Signal to Ameliorate Diet-Induced VLDL Overproduction and Insulin Resistance. Arterioscler. Thromb. Vasc. Biol. 2017; 37(12): 2252–2259.
  76. Poher A.L., Tschöp M.H., Müller T.D. Ghrelin regulation of glucose metabolism. Peptides. 2018; 100: 236–242.
  77. Prates K.V., de Oliveira J.C., Malta A.,et al. Sympathetic innervation is essential for metabolic homeostasis and pancreatic beta cell function in adult rats. Mol. Cell. Endocrinol. 2017: pii: S0303-7207(17)30516-6.
  78. Wang W., Meng X., Yang C.,et al. Brown adipose tissue activation in a rat model of Parkinson’s disease. Am. J. Physiol. Endocrinol. Metab. 2017; 313(6): E731–E736.
  79. Almundarij T.I., Gavini C.K., Novak C.M. Suppressed sympathetic outflow to skeletal muscle, muscle thermogenesis, and activity energy expenditure with calorie restriction. Physiol. Rep. 2017; 5(4): pii: e13171.
  80. Vaughn A.C., Cooper E.M., DiLorenzo P.M.,et al. Energy-dense diet triggers changes in gut microbiota, reorganization of gut brain vagal communication and increases body fat accumulation. Acta Neurobiol. Exp. (Wars). 2017; 77(1): 18–30.
  81. Brzozowski B., Mazur-Bialy A., Pajdo R.,et al. Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis. Curr. Neuropharmacol. 2016; 14(8): 892–900.
  82. Halmos T., Suba I. Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome. Orv. Hetil. 2016; 157(1): 13–22.
  83. Houlden A., Goldrick M., Brough D.,et al. Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production. Brain Behav. Immun. 2016; 57: 10–20.
  84. Sen T., Cawthon C.R., Ihde B.T.,et al. Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity. Physiol. Behav. 2017; 173:305–317.
  85. Kigerl K.A., Mostacada K., Popovich P.G. Gut Microbiota Are Disease-Modifying Factors After Traumatic Spinal Cord Injury. Neurotherapeutics. 2018; 15(1): 60–67.
  86. Toledo C., Andrade D.C., Lucero C.,et al. Contribution of peripheral and central chemoreceptors to sympatho-excitation in heart failure. J. Physiol. 2017; 595(1): 43–51.
  87. Moreira T.S., Takakura A.C., Czeisler C., Otero J.J. Respiratory and autonomic dysfunction in congenital central hypoventilation syndrome. J. Neurophysiol. 2016; 116(2): 742–752.
  88. Iturriaga R. Translating carotid body function into clinical medicine. J. Physiol. 2017.
  89. Prabhakar N.R., Peng Y.J. Oxygen Sensing by the Carotid Body: Past and Present. Adv. Exp. Med. Biol. 2017; 977: 3–8.
  90. Kouakam C., Stephan-Blanchard E., Léké A.,et al. The hypoxic test in preterm neonates reinvestigated. Pediatr. Pulmonol. 2018; 53(4): 483–491.
  91. Tubek S., Niewinski P., Reczuch K.,et al. Effects of selective carotid body stimulation with adenosine in conscious humans. J. Physiol. 2016; 594(21): 6225–6240.
  92. Niewinski P., Janczak D., Rucinski A.,et al. Carotid body resection for sympathetic modulation in systolic heart failure: results from first-in-man study. Eur. J. Heart Fail. 2017; 19(3): 391–400.
  93. Mansukhani M.P., Wang S., Somers V.K. Chemoreflex physiology and implications for sleep apnoea: insights from studiesin humans. Exp. Physiol. 2015; 100(2): 130–135.
  94. Schultz H.D., Marcus N.J., Del Rio R. Role of the Carotid Body Chemoreflex in the Pathophysiology of Heart Failure: A Perspective from Animal Studies. Adv. Exp. Med. Biol. 2015; 860: 167–185.
  95. Miller A.J., Sauder C.L., Cauffman A.E.,et al. Endurance training attenuates the increase in peripheral chemoreflex sensitivity with intermittent hypoxia. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2017; 312(2):R223–R228.
  96. Geraldes V., Carvalho M., Goncalves-Rosa N.,et al. Lead toxicity promotes autonomic dysfunction with increased chemoreceptor sensitivity. Neurotoxicology. 2016; 54: 170–177.
  97. Trembach N., Zabolotskikh I. Recruitment Maneuver in Elderly Patients with Different Peripheral Chemoreflex Sensitivity during Major Abdominal Surgery. Biomed. Res. Int. 2016; 2016: 2974852.
  98. Mirizzi G., Giannoni A., Ripoli A.,et al. Prediction of the Chemoreflex Gain by Common Clinical Variables in Heart Failure. PLoS One. 2016; 11(4): e0153510.