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The hallmark and crosstalk of immune cells after intracerebral hemorrhage: Immunotherapy perspectives.

ABSTRACT: Intracerebral hemorrhage (ICH) is one of the most dangerous types of strokes with a high morbidity and mortality rate. Currently, the treatment of ICH is not well developed, mainly because its mechanisms are still unclear. Inflammation is one of the main types of secondary injury after ICH and catalyzes the adverse consequences of ICH. A large number of immune cells are involved in neuroinflammation, such as microglia, astrocytes, oligodendrocytes, lymphocytes, macrophages, and neutrophils. Nevertheless, the characteristics and crosstalk of immune cells have not been fully elucidated. In this review, we endeavor to delve into the respective characteristics of immune cells and their interactions in neuroimmune inflammation, and further elucidate favorable immunotherapeutic approaches regarding ICH, and finally present an outlook.

SUBMITTER: Zhang W

PROVIDER: S-EPMC9877537 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The hallmark and crosstalk of immune cells after intracerebral hemorrhage: Immunotherapy perspectives.

Zhang Wenqing W Wu Qingyuan Q Hao Shilei S Chen Shengli S

Frontiers in neuroscience 20230112

Intracerebral hemorrhage (ICH) is one of the most dangerous types of strokes with a high morbidity and mortality rate. Currently, the treatment of ICH is not well developed, mainly because its mechanisms are still unclear. Inflammation is one of the main types of secondary injury after ICH and catalyzes the adverse consequences of ICH. A large number of immune cells are involved in neuroinflammation, such as microglia, astrocytes, oligodendrocytes, lymphocytes, macrophages, and neutrophils. Neve ...[more]

PMID: 36711145

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Project description:Background and purposeSpontaneous 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.MethodsWe 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.ResultsIn 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.ConclusionsAn 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.

Dataset Information

The hallmark and crosstalk of immune cells after intracerebral hemorrhage: Immunotherapy perspectives.

Publications

The hallmark and crosstalk of immune cells after intracerebral hemorrhage: Immunotherapy perspectives.

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