PDF herunterladen
CC BY-NC-ND 4.0 · J Neuroanaesth Crit Care 2021; 08(03): 163-172
DOI: 10.1055/s-0040-1721165
Review Article

Pathophysiology of Cerebral Edema—A Comprehensive Review

Tara Dalby
1   Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada
,
Elyana Wohl
2   Department of Anesthesia, Notre-Dame Hospital, Montreal, Quebec, Canada
,
Michael Dinsmore
1   Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada
,
Zoe Unger
1   Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada
,
Tumul Chowdhury
1   Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada
,
Lakshmikumar Venkatraghavan
1   Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Ontario, Canada
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Cerebral edema is a condition where an excess of cerebral water accumulates due to primary neurological or non-neurological causes. Cerebral edema complicates many brain pathologies causing additional injury often in excess of the original neurological insult. Classic descriptions divide cerebral edema into cytotoxic, vasogenic, interstitial, and osmotic subtypes. The interplay of different mechanisms is important in the clinical manifestations. Recent research has advanced our understanding of the molecular pathophysiology of cerebral edema, exposing the central role of aquaporins and specific ion channels. The aim of this review is to provide a comprehensive overview of the molecular pathophysiology of cerebral edema including unique disease specific mechanisms.

Keywords

cerebral edema - blood–brain barrier - aquaporins

Supplementary Material



Publikationsverlauf

Artikel online veröffentlicht:
03. Dezember 2020

© 2020. Indian Society of Neuroanaesthesiology and Critical Care. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Thrane AS, Rangroo Thrane V, Nedergaard M. Drowning stars: reassessing the role of astrocytes in brain edema. Trends Neurosci 2014; 37 (11) 620-628
    CrossrefPubMedGoogle Scholar
  • 2 Nakada T, Kwee IL. Fluid dynamics inside the brain barrier: current concept of interstitial flow, glymphatic flow, and cerebrospinal fluid circulation in the brain. Neuroscientist 2019; 25 (02) 155-166
    CrossrefPubMedGoogle Scholar
  • 3 Pillinger NL, Kam P. Endothelial glycocalyx: basic science and clinical implications. Anaesth Intensive Care 2017; 45 (03) 295-307
    CrossrefPubMedGoogle Scholar
  • 4 Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth 2012; 108 (03) 384-394
    CrossrefPubMedGoogle Scholar
  • 5 Ando Y, Okada H, Takemura G. et al Brain-specific ultrastructure of capillary endothelial glycocalyx and its possible contribution for blood brain barrier. Sci Rep 2018; 8 (01) 17523
    CrossrefPubMedGoogle Scholar
  • 6 Zhu J, Li X, Yin J, Hu Y, Gu Y, Pan S. Glycocalyx degradation leads to blood-brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats. J Cereb Blood Flow Metab 2018; 38 (11) 1979-1992
    CrossrefPubMedGoogle Scholar
  • 7 Keep RF, Andjelkovic AV, Xiang J. et al Brain endothelial cell junctions after cerebral hemorrhage: Changes, mechanisms and therapeutic targets. J Cereb Blood Flow Metab 2018; 38 (08) 1255-1275
    CrossrefPubMedGoogle Scholar
  • 8 Nakada T, Kwee IL, Igarashi H, Suzuki Y. Aquaporin-4 functionality and Virchow-Robin space water dynamics: physiological model for neurovascular coupling and glymphatic flow. Int J Mol Sci 2017; 18 (08) 1798
    CrossrefPubMedGoogle Scholar
  • 9 Monro A. Observations on the Structure and Function of the Nervous System. Edinburgh: Creech & Johnson 1823
  • 10 Morris AWJ, Sharp MM, Albargothy NJ. et al Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Acta Neuropathol 2016; 131 (05) 725-736
    CrossrefPubMedGoogle Scholar
  • 11 Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol 2018; 17 (11) 1016-1024
    CrossrefPubMedGoogle Scholar
  • 12 Tang G, Yang GY. Aquaporin-4: a potential therapeutic target for cerebral edema. Int J Mol Sci 2016; 17 (10) E1413
    CrossrefPubMedGoogle Scholar
  • 13 Fukuda AM, Badaut J. Aquaporin 4: a player in cerebral edema and neuroinflammation. J Neuroinflammation 2012; 9: 279
    CrossrefPubMedGoogle Scholar
  • 14 Stokum JA, Gerzanich V, Simard JM. Molecular pathophysiology of cerebral edema. J Cereb Blood Flow Metab 2016; 36 (03) 513-538
    CrossrefPubMedGoogle Scholar
  • 15 Mahajan S, Bhagat H. Cerebral oedema: pathophysiological mechanisms and experimental therapies. J Neuroanaesth Crit Care 2016; 3: 22-28
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Clément T, Rodriguez-Grande B, Badaut J. Aquaporins in brain edema. J Neurosci Res 2020; 98 (01) 9-18
    CrossrefPubMedGoogle Scholar
  • 17 Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth 2007; 99 (01) 4-9
    CrossrefPubMedGoogle Scholar
  • 18 Young W, Rappaport ZH, Chalif DJ, Flamm ES. Regional brain sodium, potassium, and water changes in the rat middle cerebral artery occlusion model of ischemia. Stroke 1987; 18 (04) 751-759
    CrossrefPubMedGoogle Scholar
  • 19 Michinaga S, Koyama Y. Pathogenesis of brain edema and investigation into anti-edema drugs. Int J Mol Sci 2015; 16 (05) 9949-9975
    CrossrefPubMedGoogle Scholar
  • 20 Hsu Y, Tran M, Linninger AA. Dynamic regulation of aquaporin-4 water channels in neurological disorders. Croat Med J 2015; 56 (05) 401-421
    CrossrefPubMedGoogle Scholar
  • 21 Manley GT, Fujimura M, Ma T. et al Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 2000; 6 (02) 159-163
    CrossrefPubMedGoogle Scholar
  • 22 Woo SK, Kwon MS, Ivanov A, Gerzanich V, Simard JM. The sulfonylurea receptor 1 (Sur1)-transient receptor potential melastatin 4 (Trpm4) channel. J Biol Chem 2013; 288 (05) 3655-3667
    CrossrefPubMedGoogle Scholar
  • 23 Simard JM, Woo SK, Gerzanich V. Transient receptor potential melastatin 4 and cell death. Pflugers Arch 2012; 464 (06) 573-582
    CrossrefPubMedGoogle Scholar
  • 24 Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V. Sulfonylurea receptor 1 in central nervous system injury: a focused review. J Cereb Blood Flow Metab 2012; 32 (09) 1699-1717
    CrossrefPubMedGoogle Scholar
  • 25 Stokum JA, Kwon MS, Woo SK. et al SUR1-TRPM4 and AQP4 form a heteromultimeric complex that amplifies ion/water osmotic coupling and drives astrocyte swelling. Glia 2018; 66 (01) 108-125
    CrossrefPubMedGoogle Scholar
  • 26 Mehta RI, Tosun C, Ivanova S. et al Sur1-Trpm4 cation channel expression in human cerebral infarcts. J Neuropathol Exp Neurol 2015; 74 (08) 835-849
    CrossrefPubMedGoogle Scholar
  • 27 Ayata C, Ropper AH. Ischaemic brain oedema. J Clin Neurosci 2002; 9 (02) 113-124
    CrossrefPubMedGoogle Scholar
  • 28 Kuroiwa T, Miyasaka N, Fengyo Z. et al Experimental ischemic brain edema: morphological and magnetic resonance imaging findings. Neurosurg Focus 2007; 22 (05) E11
    CrossrefPubMedGoogle Scholar
  • 29 Jha RM, Kochanek PM, Simard JM. Pathophysiology and treatment of cerebral edema in traumatic brain injury. Neuropharmacology 2019; 145 (Pt B) 230-246
    CrossrefPubMedGoogle Scholar
  • 30 Donkin JJ, Vink R. Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol 2010; 23 (03) 293-299
    CrossrefPubMedGoogle Scholar
  • 31 Winkler EA, Minter D, Yue JK, Manley GT. Cerebral edema in traumatic brain injury pathophysiology and prospective therapeutic targets. Neurosurg Clin N Am 2016; 27 (04) 473-488
    CrossrefPubMedGoogle Scholar
  • 32 Sorby-Adams AJ, Marcoionni AM, Dempsey ER, Woenig JA, Turner RJ. The role of neurogenic inflammation in blood-brain barrier disruption and development of cerebral oedema following acute central nervous system (CNS) injury. Int J Mol Sci 2017; 18 (08) 1788
    CrossrefPubMedGoogle Scholar
  • 33 Stocchetti N, Maas AI. Traumatic intracranial hypertension. N Engl J Med 2014; 370 (22) 2121-2130
    CrossrefPubMedGoogle Scholar
  • 34 Gorse KM, Lantzy MK, Lee ED, Lafrenaye AD. Transient receptor potential melastatin 4 induces astrocyte swelling but not death after diffuse traumatic brain injury. J Neurotrauma 2018; 35 (14) 1694-1704
    CrossrefPubMedGoogle Scholar
  • 35 Volbers B, Giede-Jeppe A, Gerner ST. et al Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage. Neurology 2018; 90 (12) e1005-e1012
    CrossrefPubMedGoogle Scholar
  • 36 Ironside N, Chen CJ, Ding D. Mayer SA, Connolly ES Jr. Perihematomal edema after spontaneous intracerebral hemorrhage. Stroke 2019; 50 (06) 1626-1633
    CrossrefPubMedGoogle Scholar
  • 37 Zheng H, Chen C, Zhang J, Hu Z. Mechanism and therapy of brain edema after intracerebral hemorrhage. Cerebrovasc Dis 2016; 42 (3-4) 155-169
    CrossrefPubMedGoogle Scholar
  • 38 Yehya M, Torbey MT. The role of mast cells in intracerebral hemorrhage. Neurocrit Care 2018; 28 (03) 288-295
    CrossrefPubMedGoogle Scholar
  • 39 Bodmer D, Vaughan KA, Zacharia BE, Hickman ZL, Connolly ES. The molecular mechanisms that promote edema after intracerebral hemorrhage. Transl Stroke Res 2012; 3, Suppl 1) 52-61
    CrossrefPubMedGoogle Scholar
  • 40 Sehba FA, Hou J, Pluta RM, Zhang JH. The importance of early brain injury after subarachnoid hemorrhage. Prog Neurobiol 2012; 97 (01) 14-37
    CrossrefPubMedGoogle Scholar
  • 41 Claassen J, Carhuapoma JR, Kreiter KT, Du EY, Connolly ES, Mayer SA. Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome. Stroke 2002; 33 (05) 1225-1232
    CrossrefPubMedGoogle Scholar
  • 42 Weimer JM, Jones SE, Frontera JA. Acute cytotoxic and vasogenic edema after subarachnoid hemorrhage: a quantitative MRI study. Am J Neuroradiol 2017; 38 (05) 928-934
    CrossrefPubMedGoogle Scholar
  • 43 Hayman EG, Wessell A, Gerzanich V, Sheth KN, Simard JM. Mechanisms of global cerebral edema formation in aneurysmal subarachnoid hemorrhage. Neurocrit Care 2017; 26 (02) 301-310
    CrossrefPubMedGoogle Scholar
  • 44 Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 2006; 26 (11) 1341-1353
    CrossrefPubMedGoogle Scholar
  • 45 Tosun C, Kurland DB, Mehta R. et al Inhibition of the Sur1-Trpm4 channel reduces neuroinflammation and cognitive impairment in subarachnoid hemorrhage. Stroke 2013; 44 (12) 3522-3528
    CrossrefPubMedGoogle Scholar
  • 46 Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol 2014; 10 (01) 44-58
    CrossrefPubMedGoogle Scholar
  • 47 Østergaard L, Aamand R, Karabegovic S. et al The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. J Cereb Blood Flow Metab 2013; 33 (12) 1825-1837
    CrossrefPubMedGoogle Scholar
  • 48 Ahn SH, Savarraj JP, Pervez M. et al The subarachnoid hemorrhage early brain edema score predicts delayed cerebral ischemia and clinical outcomes. Neurosurgery 2018; 83 (01) 137-145
    CrossrefPubMedGoogle Scholar
  • 49 Murayi R, Chittiboina P. Glucocorticoids in the management of peritumoral brain edema: a review of molecular mechanisms. Childs Nerv Syst 2016; 32 (12) 2293-2302
    CrossrefPubMedGoogle Scholar
  • 50 Heiss JD, Papavassiliou E, Merrill MJ. et al Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. J Clin Invest 1996; 98 (06) 1400-1408
    CrossrefPubMedGoogle Scholar
  • 51 Stummer W. Mechanisms of tumor-related brain edema. Neurosurg Focus 2007; 22 (05) E8
    CrossrefPubMedGoogle Scholar
  • 52 Gerstner ER, Duda DG, di Tomaso E. et al VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol 2009; 6 (04) 229-236
    CrossrefPubMedGoogle Scholar
  • 53 Dubois LG, Campanati L, Righy C. et al Gliomas and the vascular fragility of the blood brain barrier. Front Cell Neurosci 2014; 8: 418
    CrossrefPubMedGoogle Scholar
  • 54 Reulen HJ, Graber S, Huber P, Ito U. Factors affecting the extension of peritumoural brain oedema. A CT-study. Acta Neurochir (Wien) 1988; 95 (1-2) 19-24
    CrossrefPubMedGoogle Scholar
  • 55 Papadopoulos MC, Saadoun S. Key roles of aquaporins in tumor biology. Biochim Biophys Acta 2015; 1848 (10 Pt B) 2576-2583
    CrossrefPubMedGoogle Scholar
  • 56 Scott TR, Kronsten VT, Hughes RD, Shawcross DL. Pathophysiology of cerebral oedema in acute liver failure. World J Gastroenterol 2013; 19 (48) 9240-9255
    CrossrefPubMedGoogle Scholar
  • 57 Paschoal FM Junior, Nogueira RC, Oliveira ML. et al Cerebral hemodynamic and metabolic changes in fulminant hepatic failure. Arq Neuropsiquiatr 2017; 75 (07) 470-476
    CrossrefPubMedGoogle Scholar
  • 58 Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology 2006; 44 (04) 788-794
    CrossrefPubMedGoogle Scholar
  • 59 Nguyen JH. Blood-brain barrier in acute liver failure. Neurochem Int 2012; 60 (07) 676-683
    CrossrefPubMedGoogle Scholar
  • 60 Sekhon MS, Ainslie PN, Griesdale DE. Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a “two-hit” model. Crit Care 2017; 21 (01) 90
    CrossrefPubMedGoogle Scholar
  • 61 Harukuni I, Bhardwaj A. Mechanisms of brain injury after global cerebral ischemia. Neurol Clin 2006; 24 (01) 1-21
    CrossrefPubMedGoogle Scholar
  • 62 Rhee CJ, da CS Costa, Austin T, Brady KM, Czosnyka M, Lee JK. Neonatal cerebrovascular autoregulation. Pediatr Res 2018; 84 (05) 602-610
    CrossrefPubMedGoogle Scholar
  • 63 Sagoo RS, Hutchinson CE, Wright A. et al Birmingham Medical Research and Expedition Society. Magnetic Resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema. J Cereb Blood Flow Metab 2017; 37 (01) 319-331
    CrossrefPubMedGoogle Scholar
  • 64 Hackett PH, Roach RC. High-altitude illness. N Engl J Med 2001; 345 (02) 107-114
    CrossrefPubMedGoogle Scholar
  • 65 Hackett PH, Yarnell PR, Weiland DA, Reynard KB. Acute and evolving MRI of high-altitude cerebral edema: microbleeds, edema, and pathophysiology. AJNR Am J Neuroradiol 2019; 40 (03) 464-469
    PubMedGoogle Scholar