Hostname: page-component-68945f75b7-76l5x Total loading time: 0 Render date: 2024-08-06T09:33:14.445Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of Anesthetic Agents on Blood Brain Barrier Integrity: A Systematic Review

Published online by Cambridge University Press:  10 November 2022

Abanoub Aziz Rizk ,
Eric Plitman ,
Pooja Senthil ,
Lashmi Venkatraghavan Open the ORCID record for Lashmi Venkatraghavan [Opens in a new window]  and
Tumul Chowdhury Open the ORCID record for Tumul Chowdhury [Opens in a new window]
Abanoub Aziz Rizk
Affiliation:
Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Eric Plitman
Affiliation:
Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
Pooja Senthil
Affiliation:
Faculty of Science, McMaster University, Hamilton, Toronto, Ontario, Canada
Lashmi Venkatraghavan
Affiliation:
Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
Tumul Chowdhury*
Affiliation:
Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
*
Corresponding author: Tumul Chowdhury MD, DM, FRCPC, Consultant Anesthesiologist, Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. Email: Tumul.Chowdhury@uhn.ca
Get access Rights & Permissions [Opens in a new window]

Abstract:

Background:

The blood brain barrier (BBB) is a highly selective permeable barrier that separates the blood and the central nervous system. Anesthesia is an integral part of surgery, and there is little known about the impact of anesthetics on the BBB. Therefore, it is imperative to explore reversible or modifiable variables such as anesthetic agents that influence BBB integrity. We aimed to synthesize the literature pertaining to the various effects of anesthetics on the BBB.

Methods:

MEDLINE, Embase, and Cochrane were searched from inception up to September 2022.

Results:

A total of 14 articles met inclusion into the review. The articles included nine randomized control studies (64.3%) and five quasi-experimental studies (35.7%). Twelve studies used volatile anesthetics, one study used fentanyl intravenously, and one study used pentobarbital or ketamine intraperitoneally. BBB structural deficits following the administration of an anesthetic agent included ultrastructural deficits, decreases in tight junctions, and decreases in BBB components. BBB functional deficits included permeability increases following exposure to volatile anesthetics. However, two studies found decreased permeability after fentanyl, pentobarbital, or ketamine exposure. Moreover, the impact of anesthetics on the BBB seems to be related to the duration of exposure. Notably, study findings also suggest that changes following anesthetic exposure demonstrate some reversibility over the short-term.

Conclusion:

Overall, our systematic review highlights interesting findings pertaining to the impact of anesthetic agents on BBB integrity in previously healthy models. These findings and mechanisms should inspire future work to aid practitioners and healthcare teams potentially better care for patients.

Résumé :

RÉSUMÉ :

Effets des anesthésiques sur l’intégrité de la barrière hématoencéphalique : résultats d’une synthèse.

Contexte :

La barrière hématoencéphalique (BHE) est une structure perméable, très sélective, qui isole le système nerveux central de la circulation sanguine. L’anesthésie fait partie intégrante de la chirurgie, et on en sait peu sur l’influence des anesthésiques sur la BHE. Aussi est-il impérieux d’étudier les variables réversibles ou modifiables, par exemple les anesthésiques, qui influent sur l’intégrité de la BHE. L’étude visait donc à dresser une synthèse de la documentation médicale sur les différents effets des anesthésiques sur la BHE.

Méthode :

Une recherche a été effectuée dans les bases de données MEDLINE, Embase et Cochrane, depuis leur constitution jusqu’à septembre 2022.

Résultats :

Au total, 14 articles respectaient les critères de sélection de l’étude en vue de la synthèse : 9 d’entre eux (64,3 %) faisaient état d’études comparatives à répartition aléatoire et 5 (35,7 %), d’études quasi expérimentales. Dans douze études, on avait administré des anesthésiques volatils; dans une, du fentanyl par voie intraveineuse; et, dans une autre, du pentobarbital ou de la kétamine par voie intrapéritonéale. Les failles structurales de la BHE observées après l’administration des anesthésiques comprenaient des faiblesses ultrastructurales, un relâchement des jonctions serrées et une diminution des composants de la BHE. Parmi les troubles fonctionnels de la BHE, il y avait une augmentation de la perméabilité à la suite de l’exposition aux anesthésiques volatiles. Par contre, une diminution de la perméabilité avait été observée, dans deux études, après l’administration de fentanyl, de pentobarbital ou de kétamine. De plus, les effets des anesthésiques sur la BHE semblaient liés à la durée d’exposition. Point digne de mention : d’après des études, il se produirait, à court terme, une certaine réversibilité des modifications consécutives à l’exposition aux anesthésiques.

Conclusion :

Dans l’ensemble, les résultats de la revue systématique font ressortir des changements intéressants, liés à l’action des anesthésiques sur l’intégrité de la BHE chez des sujets antérieurement en bonne santé. Les constations et les mécanismes qui s’en dégagent devraient donner lieu à d’autres travaux de recherche dans le but d’aider les praticiens et les équipes de soins de santé à améliorer potentiellement les soins aux patients.

Keywords

AnesthesiaAnimal modelsBlood brain barrierCognitive impairmentPermeabilityStructure
Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 50 , Issue 6 , November 2023 , pp. 897 - 904
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Yang, S, Gu, C, Mandeville, ET, et al. Anesthesia and surgery impair blood-brain barrier and cognitive function in mice. Front Immunol. 2017;8:902.CrossRefGoogle ScholarPubMed
Acharya, NK, Goldwaser, EL, Forsberg, MM, et al. Sevoflurane and isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: possible link to postoperative delirium and cognitive decline. Brain Res. 2015;1620:29–41.CrossRefGoogle ScholarPubMed
Netto, JP, Iliff, J, Stanimirovic, D, et al. Neurovascular unit: basic and clinical imaging with emphasis on advantages of ferumoxytol. Neurosurgery. 2018;82:770–80.CrossRefGoogle ScholarPubMed
Simöes Da Gama, C, Morin-Brureau, M. Study of BBB dysregulation in neuropathogenicity using integrative human model of blood-brain barrier. Front Cell Neurosci. 2022;10; 16:863836.CrossRefGoogle Scholar
Cao, Y, Ni, C, Li, Z, et al. Isoflurane anesthesia results in reversible ultrastructure and occludin tight junction protein expression changes in hippocampal blood-brain barrier in aged rats. Neurosci Lett. 2015;587:51–6.CrossRefGoogle ScholarPubMed
Zhu, H, Liu, W, Fang, H. Inflammation caused by peripheral immune cells across into injured mouse blood brain barrier can worsen postoperative cognitive dysfunction induced by isoflurane. BMC Cell Biol. 2018;19:23.CrossRefGoogle ScholarPubMed
Hu, N, Wang, C, Zheng, Y, et al. The role of the Wnt/β-catenin-Annexin A1 pathway in the process of sevoflurane-induced cognitive dysfunction. J Neurochem. 2016;137:240–52.CrossRefGoogle ScholarPubMed
He, HJ, Wang, Y, Le, Y, et al. Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. CNS Neurosci Ther. 2012;18:994–1002.CrossRefGoogle ScholarPubMed
Profaci, CP, Munji, RN, Pulido, RS, Daneman, R. The blood-brain barrier in health and disease: important unanswered questions. J Exp Med. 2020;217.CrossRefGoogle ScholarPubMed
Ghoneim, MM, Block, RI. Clinical, methodological and theoretical issues in the assessment of cognition after anaesthesia and surgery: a review. Eur J Anaesthesiol. 2012;29:409–22.CrossRefGoogle ScholarPubMed
Murad, MH, Sultan, S, Haffar, S, Bazerbachi, F. Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med. 2018;23:60–3.CrossRefGoogle ScholarPubMed
Sun, Z, Satomoto, M, Adachi, YU, Makita, K. Blood-brain barrier disruption caused by neonatal sevoflurane-induced depends on exposure time and is reversible in mice. Korean J Anesthesiol. 2019;72:389–91.CrossRefGoogle ScholarPubMed
Wang, B, Li, S, Cao, X, et al. Blood-brain barrier disruption leads to postoperative cognitive dysfunction. Curr Neurovasc Res. 2017;14:359–67.CrossRefGoogle ScholarPubMed
Johansson, BB, Linder, LE. Cerebrovascular permeability to protein in the rat during nitrous oxide anaesthesia at various blood pressure levels. Acta Anaesthesiol Scand. 1978;22:463–6.CrossRefGoogle ScholarPubMed
Chi, OZ, Anwar, M, Sinha, AK, Wei, HM, Klein, SL, Weiss, HR. Effects of isoflurane on transport across the blood-brain barrier. Anesthesiology. 1992;76:426–31.CrossRefGoogle ScholarPubMed
Nemoto, EM, Stezoski, SW, MacMurdo, D. Glucose transport across the rat blood-brain barrier during anesthesia. Anesthesiology. 1978;49:170–6.CrossRefGoogle ScholarPubMed
Cao, Y, Li, Z, Li, H, et al. Hypoxia-inducible factor-1α is involved in isoflurane-induced blood-brain barrier disruption in aged rats model of POCD. Behav Brain Res. 2018;339:39–46.CrossRefGoogle ScholarPubMed
Zheng, JW, Meng, B, Li, XY, Lu, B, Wu, GR, Chen, JP. NF-κB/P65 signaling pathway: a potential therapeutic target in postoperative cognitive dysfunction after sevoflurane anesthesia. Eur Rev Med Pharmacol Sci. 2017;21:394–407.Google ScholarPubMed
Chi, OZ, Wei, HM, Anwar, M, Sinha, AK, Klein, SL, Weiss, HR. Effects of fentanyl on alpha-aminoisobutyric acid transfer across the blood-brain barrier. Anesth Analg. 1992;75:31–6.CrossRefGoogle ScholarPubMed
Saija, A, Princi, P, De Pasquale, R, Costa, G. Modifications of the permeability of the blood-brain barrier and local cerebral metabolism in pentobarbital- and ketamine-anaesthetized rats. Neuropharmacology. 1989;28:997–1002.CrossRefGoogle ScholarPubMed
Pruka, A. Research hub: evidence based practice toolkit: levels of evidence, 2013.Google Scholar
Hu, N, Guo, D, Wang, H, et al. Involvement of the blood-brain barrier opening in cognitive decline in aged rats following orthopedic surgery and high concentration of sevoflurane inhalation. Brain Res. 2014;1551:13–24.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Rizk et al. supplementary material

Rizk et al. supplementary material

Download Rizk et al. supplementary material(PDF)
PDF 950.2 KB