Shtaya, A; Bridges, LR; Williams, R; Trippier, S; Zhang, L; Pereira, AC; Nicoll, JAR; Boche, D; Hainsworth, AH
(2021)
Innate Immune Anti-Inflammatory Response in Human Spontaneous Intracerebral Hemorrhage.
Stroke, 52 (11).
pp. 3613-3623.
ISSN 1524-4628
https://doi.org/10.1161/STROKEAHA.121.034673
SGUL Authors: Hainsworth, Atticus Henry Shtaya, Anan BY
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Abstract
Background and Purpose: Spontaneous intracerebral hemorrhage (sICH) is a common form of hemorrhagic stroke, with high mortality and morbidity. Pathophysiological mechanisms in sICH are poorly understood and treatments limited. Neuroinflammation driven by microglial-macrophage activation contributes to brain damage post-sICH. We aim to test the hypothesis that an anti-inflammatory (repair) process occurs in parallel with neuroinflammation in clinical sICH. Methods: We performed quantitative analysis of immunohistochemical markers for microglia and macrophages (Iba1, CD68, TMEM119, CD163, and CD206) in brain tissue biospecimens 1 to 12 days post-sICH and matched control cases. In a parallel, prospective group of patients, we assayed circulating inflammatory markers (CRP [C-reactive protein], total white cell, and monocyte count) over 1 to 12 days following sICH. Results: In 27 supratentorial sICH cases (n=27, median [interquartile range] age: 59 [52–80.5], 14F/13M) all microglia-macrophage markers increased post-sICH, relative to control brains. Anti-inflammatory markers (CD163 and CD206) were elevated alongside proinflammatory markers (CD68 and TMEM119). CD163 increased progressively post-sICH (15.0-fold increase at 7–12 days, P<0.001). CD206 increased at 3 to 5 days (5.2-fold, P<0.001) then returned to control levels at 7 to 12 days. The parenchymal immune response combined brain-derived microglia (TMEM119 positive) and invading monocyte-derived macrophages (CD206 positive). In a prospective sICH patient cohort (n=26, age 74 [66–79], National Institutes of Health Stroke Scale on admission: 8 [4–17]; 14F/12M) blood CRP concentration and monocyte density (but not white blood cell) increased post-sICH. CRP increased from 0 to 2 to 3 to 5 days (8.3-fold, P=0.020) then declined at 7 to 12 days. Monocytes increased from 0 to 2 to 3 to 5 days (1.8-fold, P<0.001) then declined at 7 to 12 days. Conclusions: An anti-inflammatory pathway, enlisting native microglia and blood monocytes, occurs alongside neuroinflammation post-sICH. This novel pathway offers therapeutic targets and a window of opportunity (3–5 days post-sICH) for delivery of therapeutics via invading monocytes.
Item Type: | Article | |||||||||||||||||||||||||||||||||
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Additional Information: | Correction available at https://doi.org/10.1161/STR.0000000000000405 © 2021 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes. | |||||||||||||||||||||||||||||||||
Keywords: | immunity, inflammation, macrophages, microglia, monocytes, Adult, Aged, Aged, 80 and over, Cerebral Hemorrhage, Female, Hemorrhagic Stroke, Humans, Immunity, Innate, Macrophages, Male, Microglia, Middle Aged, Neuroinflammatory Diseases, Microglia, Macrophages, Humans, Cerebral Hemorrhage, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Immunity, Innate, Hemorrhagic Stroke, Neuroinflammatory Diseases, immunity, inflammation, macrophages, microglia, monocytes, 1103 Clinical Sciences, 1102 Cardiorespiratory Medicine and Haematology, 1109 Neurosciences, Neurology & Neurosurgery | |||||||||||||||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) | |||||||||||||||||||||||||||||||||
Journal or Publication Title: | Stroke | |||||||||||||||||||||||||||||||||
ISSN: | 1524-4628 | |||||||||||||||||||||||||||||||||
Language: | eng | |||||||||||||||||||||||||||||||||
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Publisher License: | Creative Commons: Attribution-Noncommercial 4.0 | |||||||||||||||||||||||||||||||||
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PubMed ID: | 34281379 | |||||||||||||||||||||||||||||||||
Web of Science ID: | WOS:000710623500042 | |||||||||||||||||||||||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/113274 | |||||||||||||||||||||||||||||||||
Publisher's version: | https://doi.org/10.1161/STROKEAHA.121.034673 |
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