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Systemic inflammation after stroke: implications for post-stroke comorbidities.

ABSTRACT: Immunological mechanisms have come into the focus of current translational stroke research, and the modulation of neuroinflammatory pathways has been identified as a promising therapeutic approach to protect the ischemic brain. However, stroke not only induces a local neuroinflammatory response but also has a profound impact on systemic immunity. In this review, we will summarize the consequences of ischemic stroke on systemic immunity at all stages of the disease, from onset to long-term outcome, and discuss underlying mechanisms of systemic brain-immune communication. Furthermore, since stroke commonly occurs in patients with multiple comorbidities, we will also overview the current understanding of the potential role of systemic immunity in common stroke-related comorbidities, such as cardiac dysfunction, atherosclerosis, diabetes, and infections. Finally, we will highlight how targeting systemic immunity after stroke could improve long-term outcomes and alleviate comorbidities of stroke patients.

SUBMITTER: Simats A

PROVIDER: S-EPMC9449596 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Systemic inflammation after stroke: implications for post-stroke comorbidities.

Simats Alba A Liesz Arthur A

EMBO molecular medicine 20220815 9

Immunological mechanisms have come into the focus of current translational stroke research, and the modulation of neuroinflammatory pathways has been identified as a promising therapeutic approach to protect the ischemic brain. However, stroke not only induces a local neuroinflammatory response but also has a profound impact on systemic immunity. In this review, we will summarize the consequences of ischemic stroke on systemic immunity at all stages of the disease, from onset to long-term outcom ...[more]

PMID: 35971650

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Project description:IntroductionPost-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.MethodsIn this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6-12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment.ResultsSRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1β serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Project description:BackgroundSystemic immune-inflammation index (SII) is a novel biomarker of growing interest in predicting stroke. The aim of this study was to investigate its predictive value and explore its effect modification on folic acid supplement for stroke primary prevention in a Chinese population with hypertension.MethodsA total of 10,013 participants from the China Stroke Primary Prevention Trial with available neutrophil, platelet and lymphocyte count were included, including 5,019 subjects in the enalapril group and 4,994 in the enalapril-folic acid group. SII was calculated as (platelet × neutrophil)/lymphocyte. The primary endpoint was first stroke. Cox proportional hazards models were used to evaluate the association between SII and first stroke.ResultsA U-shape association between SII and first stroke risk was observed in enalapril group. Compared with the reference group (Quartile 2: 335.1 to <443.9 × 109 cell/L), the adjusted HRs were 1.68 (95 % CI: 1.06-2.66, P = 0.027) in Quartile 1 (<335.1 × 109 cell/L), 1.43 (95 % CI: 0.90-2.27, P = 0.126) in Quartile 3 (443.9 to <602.6 × 109 cell/L), and 1.61 (95 % CI: 1.03-2.51, P = 0.035) in Quartile 4 (≥602.6 × 109 cell/L). There was no significant association between SII and first stroke in the enalapril-folic acid group, with adjusted HR of 0.92 (95%CI: 0.54-1.56, P = 0.749) in Quartile 1(<334.7 × 109 cell/L), 1.36 (95%CI: 0.84-2.21, P = 0.208) in Quartile 3 (446.2 to <595.2 × 109 cell/L), and 1.41 (95%CI: 0.87-2.27, P = 0.163) in Quartile 4 (≥595.2 × 109 cell/L). A remarkable interaction between baseline SII and folic acid supplement for stroke prevention was observed, with particularly reduced risk by 44 % (HR: 0.56; 95 % CI: 0.34-0.90; P = 0.018) in the lowest SII group (P for interaction = 0.041).ConclusionsAmong Chinese adults with hypertension, both low and high SII at baseline predicted increased first stroke risk. And compensatory folic acid particularly reduced first stroke risk in the lowest SII subgroup.

Project description:BackgroundNovel preventive therapies are needed for postoperative delirium, which especially affects older patients. A mouse model is presented that captures inflammation-associated cortical slow wave activity (SWA) observed in patients, allowing exploration of the mechanistic role of prostaglandin-adenosine signalling.MethodsEEG and cortical cytokine measurements (interleukin 6, monocyte chemoattractant protein-1) were obtained from adult and aged mice. Behaviour, SWA, and functional connectivity were assayed before and after systemic administration of lipopolysaccharide (LPS)+piroxicam (cyclooxygenase inhibitor) or LPS+caffeine (adenosine receptor antagonist). To avoid the confounder of inflammation-driven changes in movement which alter SWA and connectivity, electrophysiological recordings were classified as occurring during quiescence or movement, and propensity score matching was used to match distributions of movement magnitude between baseline and post-LPS administration.ResultsLPS produces increases in cortical cytokines and behavioural quiescence. In movement-matched data, LPS produces increases in SWA (likelihood-ratio test: χ2(4)=21.51, P<0.001), but not connectivity (χ2(4)=6.39, P=0.17). Increases in SWA associate with interleukin 6 (P<0.001) and monocyte chemoattractant protein-1 (P=0.001) and are suppressed by piroxicam (P<0.001) and caffeine (P=0.046). Aged animals compared with adult animals show similar LPS-induced SWA during movement, but exaggerated cytokine response and increased SWA during quiescence.ConclusionsCytokine-SWA correlations during wakefulness are consistent with observations in patients with delirium. Absence of connectivity effects after accounting for movement changes suggests decreased connectivity in patients is a biomarker of hypoactivity. Exaggerated effects in quiescent aged animals are consistent with increased hypoactive delirium in older patients. Prostaglandin-adenosine signalling may link inflammation to neural changes and hence delirium.

Project description:BackgroundSystemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD. Here, we aimed to determine whether impaired SUV39H1 expression in COPD patients associated with neutrophilic/eosinophilic inflammation responses and comorbidities.MethodsA total of 213 COPD patients and 13 healthy controls were recruited from the Shuang Ho Hospital, Taipei Medical University. SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy and 30 COPD participants were measured by immunoblotting. We classified the patients into two groups based on low (fold change, FC < 0.5) and high SUV39H1 expression (FC ≥ 0.5) compared to normal controls. Clinical outcomes including neutrophil or eosinophil counts associated with SUV39H1-related inflammation were evaluated by Chi square analyses or Mann-Whitney U test. The correlations between the percentage of neutrophils and number of COPD comorbidities or Charlson Comorbidity Index (CCI) scores were performed by Spearman's rank analysis.ResultsLow SUV39H1 expression group had high neutrophil counts relative to high SUV39H1expression group. In the COPD cohort, the high comorbidity group (≥ 2 comorbidities) had higher counts of whole white blood cell (WBC) and neutrophil, and lower proportion of eosinophil and eosinophil/neutrophil, as compared with low comorbidity group (0 and 1 comorbidities). The quantity of neutrophils was associated with COPD comorbidities (Spearman's r = 0.388, p < 0.001), but not with CCI scores. We also found that the high comorbidity group had more exacerbations per year compared with low comorbidity group (1.5 vs. 0.9 average exacerbations, p = 0.005). However, there were no significant differences between groups with these non-frequent (0-1 exacerbation) and frequent exacerbations per year (> 1 exacerbation) in numbers of WBC and proportion of neutrophils, eosinophils or eosinophil/neutrophil. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities.ConclusionBlood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.

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Systemic inflammation after stroke: implications for post-stroke comorbidities.

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Systemic inflammation after stroke: implications for post-stroke comorbidities.

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