eprintid: 10060370
rev_number: 20
eprint_status: archive
userid: 608
dir: disk0/10/06/03/70
datestamp: 2018-11-05 11:23:33
lastmod: 2021-10-09 22:35:54
status_changed: 2018-11-05 11:23:33
type: article
metadata_visibility: show
creators_name: Danielson, M
creators_name: Reinsfelt, B
creators_name: Westerlind, A
creators_name: Zetterberg, H
creators_name: Blennow, K
creators_name: Ricksten, S-E
title: Effects of methylprednisolone on blood-brain barrier and cerebral inflammation in cardiac surgery—a randomized trial
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: Aortic valve replacement, Cardiopulmonary bypass, Cerebrospinal fluid, Neuroinflammatory response, Methylprednisolone
note: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
abstract: BACKGROUND: Cognitive dysfunction is a frequent complication to open-heart surgery. Cerebral inflammation caused by blood-brain barrier (BBB) dysfunction due to a systemic inflammatory response is considered a possible etiology. The effects of the glucocorticoid, methylprednisolone, on cerebrospinal fluid (CSF) markers of BBB function, neuroinflammation, and brain injury in patients undergoing cardiac surgery with cardiopulmonary bypass were studied. METHODS: In this prospective, randomized, blinded study, 30 patients scheduled for elective surgical aortic valve replacement were randomized to methylprednisolone 15 mg/kg (n = 15) or placebo (n = 15) as a bolus dose administered after induction of anesthesia. CSF and blood samples were obtained the day before and 24 h after surgery for assessment of systemic and brain inflammation (interleukin-6, interleukin-8, tumor necrosis factor-alpha), axonal injury (total-tau, neurofilament light chain protein), neuronal injury (neuron-specific enolase), astroglial injury (S-100B, glial fibrillary acidic protein), and the BBB integrity (CSF/serum albumin ratio). RESULTS: In the control group, there was a 54-fold and 17-fold increase in serum interleukin-6 and interleukin-8, respectively. This systemic activation of the inflammatory cytokines was clearly attenuated by methylprednisolone (p < 0.001). The increase of the CSF levels of the astroglial markers was not affected. A postoperative BBB dysfunction was seen in both groups as the CSF/serum albumin ratio increased from 6.4 ± 8.0 to 8.0 in the placebo group (p < 0.01) and from 5.6 ± 2.3 to 7.2 in the methylprednisolone group (p < 0.01) with no difference between groups (p = 0.98). In the CSF, methylprednisolone attenuated the interleukin-6 release (p < 0.001), which could be explained by the fall in systemic interleukin-6, and the serum to CSF gradient of IL-6 seen both at baseline and after surgery. In the CSF, methylprednisolone enhanced the interleukin-8 release (p < 0.001) but did not affect postoperative changes in CSF levels of tumor necrosis factor alpha. Serum levels of S-100B and neuron-specific enolase increased in both groups with no difference between groups. CSF levels of total tau, neurofilament light chain protein, and neuron-specific enolase were not affected in any of the groups. CONCLUSIONS: Preventive treatment with high-dose methylprednisolone attenuated the systemic inflammatory response to open-heart surgery with cardiopulmonary bypass, but did not prevent or attenuate the increase in BBB permeability or the neuroinflammatory response.
date: 2018-12
date_type: published
publisher: BMC
official_url: https://doi.org/10.1186/s12974-018-1318-y
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1589492
doi: 10.1186/s12974-018-1318-y
language_elements: English
lyricists_name: Zetterberg, Henrik
lyricists_id: HZETT94
actors_name: Cuccu, Clara
actors_id: CCCUC40
actors_role: owner
full_text_status: public
publication: Journal of Neuroinflammation
volume: 15
number: 1
article_number: 283
pages: 9
issn: 1742-2094
citation:        Danielson, M;    Reinsfelt, B;    Westerlind, A;    Zetterberg, H;    Blennow, K;    Ricksten, S-E;      (2018)    Effects of methylprednisolone on blood-brain barrier and cerebral inflammation in cardiac surgery—a randomized trial.                   Journal of Neuroinflammation , 15  (1)    , Article 283.  10.1186/s12974-018-1318-y <https://doi.org/10.1186/s12974-018-1318-y>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10060370/1/Zetterberg_Effects%20of%20methylprednisolone%20on%20blood-brain%20barrier%20and%20cerebral%20inflammation%20in%20cardiac%20surgery-a%20randomized%20trial_VoR.pdf