Skip to main content
SpringerLink
Log in

Brain

  • Chapter
  • First Online:
Management of Dysregulated Immune Response in the Critically Ill

Part of the book series: Lessons from the ICU ((LEICU))

  • 554 Accesses

Abstract

Apart from other mechanisms of action, including consequences of coagulation disturbances, hypoxia, hypoperfusion, secondary injuries, sedation, etc., it is increasingly recognized that a dysregulated immune response plays an important role in the development of cerebral dysfunction in critically ill patients. The brain was long regarded as an immune-privileged organ, protected by the blood-brain barrier, but it has now become clear that the peripheral immune system may interact with the immune cells of the brain. This “neuroinflammation” may lead to synapse pathology and loss of homeostatic microglial control resulting in cerebral dysfunction that may emerge as sickness behavior, mild fluctuating cognitive dysfunction, delirium, or even coma. Moreover, it relates to persistent cognitive decline or a deterioration in mental health status, and even accelerated development of dementia. New techniques, for example positron-emission tomography (PET), enable more detailed investigations into neuroinflammation. These techniques will facilitate future research as they may be used to monitor the trajectory of neuroinflammation or to detect neuroinflammatory endpoints in phase 2 studies with promising therapeutic interventions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 69.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 99.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kelly FE, Fong K, Hirsch N, Nolan JP. Intensive care medicine is 60 years old: the history and future of the intensive care unit. Clin Med. 2014;14(4):376.

    Google Scholar 

  2. Zimmerman JE, Kramer AA, Knaus WA. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care. 2013;17(2):R81.

    PubMed  PubMed Central  Google Scholar 

  3. Desai SV, Law TJ, Needham DM. Long-term complications of critical care. Crit Care Med. 2011;39(2):371–9.

    PubMed  Google Scholar 

  4. Needham DM, Davidson J, Cohen H, Hopkins RO, Weinert C, Wunsch H, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders’ conference. Crit Care Med. 2012;40(2):502–9.

    PubMed  Google Scholar 

  5. Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998;351(9106):857–61.

    CAS  PubMed  Google Scholar 

  6. Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008;108(1):18–30.

    PubMed  Google Scholar 

  7. Shah FA, Pike F, Alvarez K, Angus D, Newman AB, Lopez O, et al. Bidirectional relationship between cognitive function and pneumonia. Am J Respir Crit Care Med. 2013;188(5):586–92.

    PubMed  PubMed Central  Google Scholar 

  8. Hughes CG, Patel MB, Pandharipande PP. Pathophysiology of acute brain dysfunction: what’s the cause of all this confusion? Curr Opin Crit Care. 2012;18(5):518–26.

    PubMed  Google Scholar 

  9. Aldemir M, Özen S, Kara IH, Sir A, Baç B. Predisposing factors for delirium in the surgical intensive care unit. Crit Care. 2001;5(5):265–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001;27(8):1297–304.

    CAS  PubMed  Google Scholar 

  11. McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc. 2003;51(5):591–8.

    PubMed  Google Scholar 

  12. Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y. Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007;33(1):66–73.

    PubMed  Google Scholar 

  13. van den Boogaard M, Schoonhoven L, van der Hoeven JG, van Achterberg T, Pickkers P. Incidence and short-term consequences of delirium in critically ill patients: a prospective observational cohort study. Int J Nurs Stud. 2012;49(7):775–83.

    PubMed  Google Scholar 

  14. Widmann CN, Heneka MT. Long-term cerebral consequences of sepsis. Lancet Neurol. 2014;13(6):630–6.

    PubMed  Google Scholar 

  15. Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol. 2012;8(10):557–66.

    CAS  PubMed  Google Scholar 

  16. Geense WW, Zegers M, Peters MAA, Ewalds E, Simons KS, Vermeulen H, et al. New physical, mental, and cognitive problems 1 year after ICU admission: a prospective multicenter study. Am J Respir Crit Care Med. 2021;203(12):1512–21.

    PubMed  Google Scholar 

  17. Honarmand K, Lalli RS, Priestap F, Chen JL, McIntyre CW, Owen AM, et al. Natural history of cognitive impairment in critical illness survivors. A systematic review. Am J Respir Crit Care Med. 2020;202(2):193–201.

    PubMed  PubMed Central  Google Scholar 

  18. Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Guerra C, Hua M, Wunsch H. Risk of a diagnosis of dementia for elderly medicare beneficiaries after intensive care. Anesthesiology. 2015;123(5):1105–12.

    PubMed  Google Scholar 

  21. Ehlenbach WJ, Hough CL, Crane PK, Haneuse SJ, Carson SS, Curtis JR, et al. Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA. 2010;303(8):763–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Wilson RS, Hebert LE, Scherr PA, Dong X, Leurgens SE, Evans DA. Cognitive decline after hospitalization in a community population of older persons. Neurology. 2012;78(13):950–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Bruce K, Smith JA, Yelland G, Robinson S. The impact of cardiac surgery on cognition. Stress Health. 2008;24(3):249–66.

    Google Scholar 

  24. Brück E, Larsson JW, Lasselin J, Bottai M, Hirvikoski T, Sundman E, et al. Lack of clinically relevant correlation between subjective and objective cognitive function in ICU survivors: a prospective 12-month follow-up study. Crit Care. 2019;23(1):253.

    PubMed  PubMed Central  Google Scholar 

  25. Peters van Ton AM, Meijer-van Leijsen EMC, Bergkamp MI, Bronkhorst EM, Pickkers P, de Leeuw FE, et al. Risk of dementia and structural brain changes following nonneurological infections during 9-year follow-up. Crit Care Med. 2022;50(4):554–64.

    PubMed  Google Scholar 

  26. Cao XZ, Ma H, Wang JK, Liu F, Wu BY, Tian AY, et al. Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats. Prog Neuro-Psychopharmacol Biol Psychiatry. 2010;34(8):1426–32.

    CAS  Google Scholar 

  27. Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology. 2007;106(3):436–43.

    PubMed  Google Scholar 

  28. Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825–73.

    PubMed  Google Scholar 

  29. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–77.

    PubMed  Google Scholar 

  30. Hoogland IC, Houbolt C, van Westerloo DJ, van Gool WA, van de Beek D. Systemic inflammation and microglial activation: systematic review of animal experiments. J Neuroinflammation. 2015;12:114.

    PubMed  PubMed Central  Google Scholar 

  31. Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, et al. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc Natl Acad Sci U S A. 2015;112(40):12468–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Woodcock EA, Hillmer AT, Sandiego CM, Maruff P, Carson RE, Cosgrove KP, et al. Acute neuroimmune stimulation impairs verbal memory in adults: a PET brain imaging study. Brain Behav Immun. 2021;91:784–7.

    CAS  PubMed  Google Scholar 

  33. Peters van Ton AM, Leijte GP, Franssen GM, Bruse N, Booij J, Doorduin J, et al. Human in vivo neuroimaging to detect reprogramming of the cerebral immune response following repeated systemic inflammation. Brain Behav Immun. 2021;95:321–9.

    CAS  PubMed  Google Scholar 

  34. Lemstra AW, Groen in’t Woud JC, Hoozemans JJ, van Haastert ES, Rozemuller AJ, Eikelenboom P, et al. Microglia activation in sepsis: a case-control study. J Neuroinflammation. 2007;4:4.

    PubMed  PubMed Central  Google Scholar 

  35. Sharshar T, Annane D, de la Grandmaison GL, Brouland JP, Hopkinson NS, Francoise G. The neuropathology of septic shock. Brain Pathol. 2004;14(1):21–33.

    PubMed  Google Scholar 

  36. Rosenberg GA. Neuroinflammatory disease: IBC meeting on neuroinflammatory disease: research and treatment strategies London, UK, 17 and 18 September 1996. Mol Med Today. 1997;3(1):12–3.

    CAS  PubMed  Google Scholar 

  37. Banks WA. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des. 2005;11(8):973–84.

    CAS  PubMed  Google Scholar 

  38. Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol. 2016;53(2):1181–94.

    CAS  PubMed  Google Scholar 

  39. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91(2):461–553.

    CAS  PubMed  Google Scholar 

  40. Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci. 2016;19(8):987–91.

    CAS  PubMed  Google Scholar 

  41. Perry VH, Holmes C. Microglial priming in neurodegenerative disease. Nat Rev Neurol. 2014;10(4):217–24.

    CAS  PubMed  Google Scholar 

  42. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007;8(1):57–69.

    CAS  PubMed  Google Scholar 

  43. Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, Kelley KW, et al. Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune system. FASEB J. 2005;19(10):1329–31.

    CAS  PubMed  Google Scholar 

  44. Michels M, Steckert AV, Quevedo J, Barichello T, Dal-Pizzol F. Mechanisms of long-term cognitive dysfunction of sepsis: from blood-borne leukocytes to glial cells. Intensive Care Med Exp. 2015;3(1):30.

    PubMed  PubMed Central  Google Scholar 

  45. Matt SM, Johnson RW. Neuro-immune dysfunction during brain aging: new insights in microglial cell regulation. Curr Opin Pharmacol. 2016;26:96–101.

    CAS  PubMed  Google Scholar 

  46. Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14(7):463–77.

    CAS  PubMed  Google Scholar 

  47. Lee M, Kang J, Jeong YJ. Risk factors for post-intensive care syndrome: a systematic review and meta-analysis. Aust Crit Care. 2020;33(3):287–94.

    PubMed  Google Scholar 

  48. Mizee MR, Miedema SS, van der Poel M, Adelia SKG, van Strien ME, et al. Isolation of primary microglia from the human post-mortem brain: effects of ante- and post-mortem variables. Acta Neuropathol Commun. 2017;5(1):16.

    PubMed  PubMed Central  Google Scholar 

  49. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010;330(6005):841–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature. 2015;518(7540):547–51.

    PubMed  Google Scholar 

  51. Melief J, Sneeboer MA, Litjens M, Ormel PR, Palmen SJ, Huitinga I, et al. Characterizing primary human microglia: a comparative study with myeloid subsets and culture models. Glia. 2016;64(11):1857–68.

    CAS  PubMed  Google Scholar 

  52. Duits FH, Martinez-Lage P, Paquet C, Engelborghs S, Lleó A, Hausner L, et al. Performance and complications of lumbar puncture in memory clinics: results of the multicenter lumbar puncture feasibility study. Alzheimers Dement. 2016;12(2):154–63.

    PubMed  Google Scholar 

  53. Poljak A, Hill M, Hall RJ, MacLullich AM, Raftery MJ, Tai J, et al. Quantitative proteomics of delirium cerebrospinal fluid. Transl Psychiatry. 2014;4:e477.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Peters van Ton AM, Verbeek MM, Alkema W, Pickkers P, Abdo WF. Downregulation of synapse-associated protein expression and loss of homeostatic microglial control in cerebrospinal fluid of infectious patients with delirium and patients with Alzheimer’s disease. Brain Behav Immun. 2020;89:656–67.

    CAS  PubMed  Google Scholar 

  55. Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov. 2010;9(12):971–88.

    CAS  PubMed  Google Scholar 

  56. Vowinckel E, Reutens D, Becher B, Verge G, Evans A, Owens T, et al. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res. 1997;50(2):345–53.

    CAS  PubMed  Google Scholar 

  57. Kuhlmann AC, Guilarte TR. Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. J Neurochem. 2000;74(4):1694–704.

    CAS  PubMed  Google Scholar 

  58. Wilms H, Claasen J, Röhl C, Sievers J, Deuschl G, Lucius R. Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: evidence from activated microglial cells in vitro. Neurobiol Dis. 2003;14(3):417–24.

    CAS  PubMed  Google Scholar 

  59. Lavisse S, Guillermier M, Hérard AS, Petit F, Delahaye M, Van Camp N, et al. Reactive astrocytes overexpress TSPO and are detected by TSPO positron emission tomography imaging. J Neurosci. 2012;32(32):10809–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Beckers L, Ory D, Geric I, Declercq L, Koole M, Kassiou M, et al. Increased expression of translocator protein (TSPO) Marks pro-inflammatory microglia but does not predict neurodegeneration. Mol Imaging Biol. 2018;20(1):94–102.

    CAS  PubMed  Google Scholar 

  61. Pannell M, Economopoulos V, Wilson TC, Kersemans V, Isenegger PG, Larkin JR, et al. Imaging of translocator protein upregulation is selective for pro-inflammatory polarized astrocytes and microglia. Glia. 2020;68(2):280–97.

    PubMed  Google Scholar 

  62. Groom GN, Junck L, Foster NL, Frey KA, Kuhl DE. PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer’s disease. J Nucl Med. 1995;36(12):2207–10.

    CAS  PubMed  Google Scholar 

  63. Bradburn S, Murgatroyd C, Ray N. Neuroinflammation in mild cognitive impairment and Alzheimer’s disease: a meta-analysis. Ageing Res Rev. 2019;50:1–8.

    CAS  PubMed  Google Scholar 

  64. Hamelin L, Lagarde J, Dorothée G, Potier MC, Corlier F, Kuhnast B, et al. Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer’s disease. Brain. 2018;141(6):1855–70.

    PubMed  Google Scholar 

  65. Kreisl WC, Lyoo CH, McGwier M, Snow J, Jenko KJ, Kimura N, et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease. Brain. 2013;136(Pt 7):2228–38.

    PubMed  PubMed Central  Google Scholar 

  66. Yasuno F, Ota M, Kosaka J, Ito H, Higuchi M, Doronbekov TK, et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry. 2008;64(10):835–41.

    CAS  PubMed  Google Scholar 

  67. Terada T, Yokokura M, Yoshikawa E, Futatsubashi M, Kono S, Konishi T, et al. Extrastriatal spreading of microglial activation in Parkinson's disease: a positron emission tomography study. Ann Nucl Med. 2016;30(8):579–87.

    CAS  PubMed  Google Scholar 

  68. Lavisse S, Goutal S, Wimberley C, Tonietto M, Bottlaender M, Gervais P, et al. Increased microglial activation in patients with Parkinson disease using [(18)F]-DPA714 TSPO PET imaging. Parkinsonism Relat Disord. 2020;82:29–36.

    PubMed  Google Scholar 

  69. Ribeiro MJ, Vercouillie J, Debiais S, Cottier JP, Bonnaud I, Camus V, et al. Could (18) F-DPA-714 PET imaging be interesting to use in the early post-stroke period? EJNMMI Res. 2014;4:28.

    PubMed  PubMed Central  Google Scholar 

  70. Coughlin JM, Wang Y, Munro CA, Ma S, Yue C, Chen S, et al. Neuroinflammation and brain atrophy in former NFL players: an in vivo multimodal imaging pilot study. Neurobiol Dis. 2015;74:58–65.

    PubMed  Google Scholar 

  71. Zurcher NR, Loggia ML, Lawson R, Chonde DB, Izquierdo-Garcia D, Yasek JE, et al. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28. Neuroimage Clin. 2015;7:409–14.

    PubMed  PubMed Central  Google Scholar 

  72. Van Weehaeghe D, Van Schoor E, De Vocht J, Koole M, Attili B, Celen S, et al. TSPO versus P2X7 as a target for neuroinflammation: an in vitro and in vivo study. J Nucl Med. 2020;61(4):604–7.

    PubMed  PubMed Central  Google Scholar 

  73. Brites D, Fernandes A. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation. Front Cell Neurosci. 2015;9:476.

    PubMed  PubMed Central  Google Scholar 

  74. Mondelli V, Vernon AC, Turkheimer F, Dazzan P, Pariante CM. Brain microglia in psychiatric disorders. Lancet Psychiatry. 2017;4(7):563–72.

    PubMed  Google Scholar 

  75. Pozzo ED, Tremolanti C, Costa B, Giacomelli C, Milenkovic VM, Bader S, et al. Microglial pro-inflammatory and anti-inflammatory phenotypes are modulated by translocator protein activation. Int J Mol Sci. 2019;20(18):4467.

    PubMed  PubMed Central  Google Scholar 

  76. Jacobs AH, Tavitian B. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab. 2012;32(7):1393–415.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Griffin ÉW, Skelly DT, Murray CL, Cunningham C. Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction. J Neurosci. 2013;33(38):15248–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Murray CL, Skelly DT, Cunningham C. Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6. J Neuroinflammation. 2011;8:50.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Hovens IB, van Leeuwen BL, Mariani MA, Kraneveld AD, Schoemaker RG. Postoperative cognitive dysfunction and neuroinflammation; cardiac surgery and abdominal surgery are not the same. Brain Behav Immun. 2016;54:178–93.

    CAS  PubMed  Google Scholar 

  80. Schaafsma W, Zhang X, van Zomeren KC, Jacobs S, Georgieva PB, Wolf SA, et al. Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing. Brain Behav Immun. 2015;48:205–21.

    CAS  PubMed  Google Scholar 

  81. Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature. 2018;556(7701):332–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Forsberg A, Cervenka S, Jonsson Fagerlund M, Rasmussen LS, Zetterberg H, Erlandsson Harris H, et al. The immune response of the human brain to abdominal surgery. Ann Neurol. 2017;81(4):572–82.

    CAS  PubMed  Google Scholar 

  83. Hamers L, Kox M, Pickkers P. Sepsis-induced immunoparalysis: mechanisms, markers, and treatment options. Minerva Anestesiol. 2015;81(4):426–39.

    CAS  PubMed  Google Scholar 

  84. Kox M, Pompe JC, Pickkers P, Hoedemaekers CW, van Vugt AB, van der Hoeven JG. Increased vagal tone accounts for the observed immune paralysis in patients with traumatic brain injury. Neurology. 2008;70(6):480–5.

    CAS  PubMed  Google Scholar 

  85. Coughlin JM, Yang T, Rebman AW, Bechtold KT, Du Y, Mathews WB, et al. Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using [(11)C]DPA-713 PET. J Neuroinflammation. 2018;15(1):346.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Nakatomi Y, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, et al. Neuroinflammation in patients with chronic fatigue syndrome/myalgic encephalomyelitis: an 11C-(R)-PK11195 PET study. J Nucl Med. 2014;55(6):945–50.

    CAS  PubMed  Google Scholar 

  87. Jutte JE, Erb CT, Jackson JC. Physical, cognitive, and psychological disability following critical illness: what is the risk? Semin Respir Crit Care Med. 2015;36(6):943–58.

    PubMed  Google Scholar 

  88. Bellesi M, de Vivo L, Chini M, Gilli F, Tononi G, Cirelli C. Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex. J Neurosci. 2017;37(21):5263.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Intensive Care Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands

    Annemieke M. Peters van Ton & Peter Pickkers

  2. Department of Intensive Care Medicine, Université libre de Bruxelles (ULB), Erasme Hospital, Brussels, Belgium

    Fabio Silvio Taccone

Authors
  1. Annemieke M. Peters van Ton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabio Silvio Taccone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Pickkers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Pickkers .

Editor information

Editors and Affiliations

  1. Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary

    Zsolt Molnar

  2. Department of Critical Care, King’s College London, Guy’s & St Thomas’ NHS Foundation Trust, London, UK

    Marlies Ostermann

  3. The Queen’s Medical Research Institute Edinburgh BioQuarter, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

    Manu Shankar-Hari

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Peters van Ton, A.M., Taccone, F.S., Pickkers, P. (2023). Brain. In: Molnar, Z., Ostermann, M., Shankar-Hari, M. (eds) Management of Dysregulated Immune Response in the Critically Ill. Lessons from the ICU. Springer, Cham. https://doi.org/10.1007/978-3-031-17572-5_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-17572-5_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-17571-8

  • Online ISBN: 978-3-031-17572-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation