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The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis

BACKGROUND: The spleen, a substantial reservoir of non-differentiated monocytes, may play a crucial role in the pathophysiology of post-ischemic inflammation and influence outcomes after ischemic stroke. AIM OF THE STUDY: To analyze splenectomy as a preclinical intervention in murine models of ische...

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Autores principales: Sternak, Marko, Glasnović, Anton, Josić, Paula, Romić, Dominik, Gajović, Srećko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508771/
https://www.ncbi.nlm.nih.gov/pubmed/36151564
http://dx.doi.org/10.1186/s12974-022-02593-w
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author Sternak, Marko
Glasnović, Anton
Josić, Paula
Romić, Dominik
Gajović, Srećko
author_facet Sternak, Marko
Glasnović, Anton
Josić, Paula
Romić, Dominik
Gajović, Srećko
author_sort Sternak, Marko
collection PubMed
description BACKGROUND: The spleen, a substantial reservoir of non-differentiated monocytes, may play a crucial role in the pathophysiology of post-ischemic inflammation and influence outcomes after ischemic stroke. AIM OF THE STUDY: To analyze splenectomy as a preclinical intervention in murine models of ischemic stroke. METHODS: Following systematic searches of PubMed, Scopus and Web of Science, a qualitative synthesis of study characteristics was performed, and the effect of splenectomy estimated by a three-level random-effects meta-analysis of infarct volumes and a conventional two-level random-effects meta-analysis of neurological deficit scores. RESULTS: Database searches identified a total of 14 studies, 13 of which were used for meta-analysis. The ischemic lesion volumes were reduced in splenectomized animals compared to the control groups (difference in standardized mean differences: − 1.42; 95% CI [− 1.98, − 0.85]; 95% PI [− 2.03, − 0.80]; I(2)((2)) = 19.04%; 95% CI [0.00%, 65.49%]; I(2)((3)) = 47.24%; 95% CI [0.00%, 85.23%]) and neurological deficit scores were improved (− 1.20; 95% CI [− 2.20, − 0.20]; 95% PI [− 4.58, 2.18]; I(2) = 77.5%; 95% CI [50.0%, 89.9%]). A subgroup analysis for infarct volumes showed that splenectomy performed prior to ischemia achieved a higher reduction of the ischemic lesion than when splenectomy was performed immediately prior or after stroke. Although the overall effect size of splenectomy could be classified as large, there was a significant presence of risks of bias, study heterogeneity, and a potential presence of publication bias. CONCLUSION: Despite limitations related to heterogeneity, risks of bias, and potential publication bias, this meta-analysis points to the spleen and its functional cell populations as promising targets for the therapeutic modulation of post-stroke inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-022-02593-w.
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spelling pubmed-95087712022-09-25 The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis Sternak, Marko Glasnović, Anton Josić, Paula Romić, Dominik Gajović, Srećko J Neuroinflammation Research BACKGROUND: The spleen, a substantial reservoir of non-differentiated monocytes, may play a crucial role in the pathophysiology of post-ischemic inflammation and influence outcomes after ischemic stroke. AIM OF THE STUDY: To analyze splenectomy as a preclinical intervention in murine models of ischemic stroke. METHODS: Following systematic searches of PubMed, Scopus and Web of Science, a qualitative synthesis of study characteristics was performed, and the effect of splenectomy estimated by a three-level random-effects meta-analysis of infarct volumes and a conventional two-level random-effects meta-analysis of neurological deficit scores. RESULTS: Database searches identified a total of 14 studies, 13 of which were used for meta-analysis. The ischemic lesion volumes were reduced in splenectomized animals compared to the control groups (difference in standardized mean differences: − 1.42; 95% CI [− 1.98, − 0.85]; 95% PI [− 2.03, − 0.80]; I(2)((2)) = 19.04%; 95% CI [0.00%, 65.49%]; I(2)((3)) = 47.24%; 95% CI [0.00%, 85.23%]) and neurological deficit scores were improved (− 1.20; 95% CI [− 2.20, − 0.20]; 95% PI [− 4.58, 2.18]; I(2) = 77.5%; 95% CI [50.0%, 89.9%]). A subgroup analysis for infarct volumes showed that splenectomy performed prior to ischemia achieved a higher reduction of the ischemic lesion than when splenectomy was performed immediately prior or after stroke. Although the overall effect size of splenectomy could be classified as large, there was a significant presence of risks of bias, study heterogeneity, and a potential presence of publication bias. CONCLUSION: Despite limitations related to heterogeneity, risks of bias, and potential publication bias, this meta-analysis points to the spleen and its functional cell populations as promising targets for the therapeutic modulation of post-stroke inflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-022-02593-w. BioMed Central 2022-09-23 /pmc/articles/PMC9508771/ /pubmed/36151564 http://dx.doi.org/10.1186/s12974-022-02593-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sternak, Marko
Glasnović, Anton
Josić, Paula
Romić, Dominik
Gajović, Srećko
The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
title The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
title_full The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
title_fullStr The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
title_full_unstemmed The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
title_short The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
title_sort effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508771/
https://www.ncbi.nlm.nih.gov/pubmed/36151564
http://dx.doi.org/10.1186/s12974-022-02593-w
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