Association Between Splenic Contraction and the Systemic Inflammatory Response After Acute Ischemic Stroke Varies with Age and Race

Zha, Alicia; Vahidy, Farhaan S; Randhawa, Jaskaren; Parsha, Kaushik; Bui, Tuan Anh; Aronowski, Jaroslaw; Savitz, Sean I

doi:10.1007/s12975-017-0596-5

Cited by 19 publications

(22 citation statements)

References 45 publications

(63 reference statements)

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“…In Alicia's study, 69.2% of patients were posterior circulation stroke, which was the heat-regulating centers located in. In terms of the time of occurrence, we found that most cases of SIRS (95.7%) occurred in the rst two days after EVT, which was consistent with the results of a previous study found that 79.1% of SIRS cases presented within 72 h after stroke [16]. A recently published study from Stanford used a single-cell mass cytometry approach to observe the systemic immune response to stroke in longitudinal blood samples from 24 patients over the course of 1 year and suggested the rst 2 days as the acute phase of in ammation [17].…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies aiming to elucidate the prevalence of SIRS have shown that approximately 18-53% of ischemic stroke patients experience SIRS in hospital [6,7,16], Boehme et al [7] found about 20% of stroke patients treated with rt-PA developed SIRS, and the presence of SIRS was positively related to initial stroke severity and poor short-term functional outcomes. However, the outcomes of SIRS in patients after EVT remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Spearman correlation analysis was adopted to explore the correlation between the severity of SIRS and clinical prognosis, and the results suggested that SIRS severity was positively correlated with NIHSS scores at discharge and mRS scores at 90-days (r = 0.237, r = 0.249, P < 0.05). [12][13][14][15][16][17][18][19]) were further compared. The neutrophil and leukomonocyte counts between these two groups were very similar (P > 0.05).…”

Section: Patient Baseline Characteristicsmentioning

confidence: 99%

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Systemic Inflammatory Response Syndrome and Outcomes in Ischemic Patients Treated with Endovascular Treatment

Yuan

Wang

et al. 2020

Preprint

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Background The occurrence of systemic inflammatory response syndrome (SIRS) is associated with poor outcomes after ischemic stroke, and the inflammatory response can be significantly attenuated by successful reperfusion, while the SIRS in patients with acute large vessel occlusion stroke (ALVOS) who underwent endovascular treatment (EVT) remain unclear. We aimed to investigate the occurrence rate, predictors, and clinical outcomes of SIRS in patients with ALVOS after EVT. Methods We retrospectively collected EVT data of patients with ALVOS from July 2014 to August 2019 in our center. SIRS in the absence of infection was defined as the presence of ≥2 of the following: (1) heart rate >90 (2) body temperature >38°C or <36°C, (3) white blood cells >12 000/mm or <4000/mm or >10% bands for >24 h or (4) respiratory rate >20. Favorable outcome was defined as obtaining a 90-day modified Rankin Scale (mRS) score ≤2. Results Among the 262 patients who received EVT, 92 (35.1%) developed SIRS, 88 (95.7%) of whom developed SIRS in the first two days after EVT. Patients who developed SIRS had a reduced favorable outcome (OR, 4.112 [95% CI, 1.705–9.920]; P=0.002) and higher mortality (OR, 25.236 [95% CI, 8.578–74.835]; P<0.001) at 90 days. Greater SIRS burden was positively correlated with NIHSS scores at discharge and mRS scores at 90 days (r=0.249, P=0.017; r=0.230, P=0.027). The development of SIRS in patients with ALOVS who underwent EVT was associated with neutrophilic leukocytosis, hyperglycemia, higher admission NIHSS scores, and worse collateral circulation. Conclusions Patients with SIRS had higher odds of poor functional outcomes and higher mortality at 90 days in the EVT-treatment setting. The severity of the inflammatory response was positively correlated with the clinical outcomes of patients. Clinically relevant associations with SIRS were neutrophilic leukocytosis, hyperglycemia and baseline stroke severity, but favorable collateral circulation was a protective factor against SIRS.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Patient Baseline Characteristicsmentioning

confidence: 99%

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Systemic Inflammatory Response Syndrome and Outcomes in Ischemic Patients Treated with Endovascular Treatment

Yuan

Wang

et al. 2020

Preprint

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“…In individuals over the age of 75, there was a negative correlation with splenic contraction and the development of SIRS at 72 h post stroke, while there was no significant connection between splenic contraction and SIRS in the younger age groups. In stroke subjects over the age of 75, the development of SIRS was higher in individuals without splenic contraction compared to those subjects with splenic contraction (71.4 vs. 46.1, respectively) [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

The splenic response to stroke: from rodents to stroke subjects

Seifert

Offner

2018

J Neuroinflammation

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BackgroundStroke is the fifth leading cause of death and the leading cause of long-term disability in the USA, costing $40.2 billion in direct and indirect costs. Globally, stroke is the second leading cause of death and has a higher prevalence in lower- and middle-income countries compared to high-income countries.The role of the spleen in stroke has been studied in rodent models of stroke and is seen as a major contributor to increased secondary neural injury after stroke. Splenectomy 2 weeks prior to ischemic and hemorrhagic stroke in mice and rats shows decreased infarct volumes. Additionally, the spleen decreases in size following stroke in rodents. Pro-inflammatory mediators are also increased in the spleen and subsequently the brain after stroke. These data in preclinical models of stroke have led stroke neurologists to look at the splenic response in stroke subjects. The outcomes of these studies suggest the spleen is responding in a similar manner in stroke subjects as it is in animal models of stroke.ConclusionAnimal models demonstrating the detrimental role of the spleen in stroke are providing strong evidence of how the spleen is responding during stroke in human subjects. This indicates treatments targeting the splenic immune response in animals could provide useful targets and treatments for stroke subjects.

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“…Interferon gamma (IFNγ) production by T cells and natural killer (NK) cells and subsequent induction of interferon inducible protein 10 (IP-10) triggers the first step in the delayed inflammatory response [ 26 , 28 – 30 ]. Clinical data have shown that this post-stroke splenic response not only occurs in human stroke patients, but also differs among patients of different ages and racial backgrounds [ 31 – 33 ].…”

Section: Introductionmentioning

confidence: 99%

Leukemia inhibitory factor modulates the peripheral immune response in a rat model of emergent large vessel occlusion

Davis

Collier

Winford

et al. 2018

J Neuroinflammation

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BackgroundThe migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke.MethodsYoung male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or PBS at 6, 24, and 48 h prior to euthanization at 72 h. Bone marrow-derived macrophages were treated with LIF (20 ng/ml) or PBS after stimulation with interferon gamma + LPS. Western blot was used to measure protein levels of CD11b, IL-12, interferon inducible protein-10, CD3, and the LIF receptor in spleen and brain tissue. ELISA was used to measure IL-10, IL-12, and interferon gamma. Isolectin was used to label activated immune cells in brain tissue sections. Statistical analysis was performed using one-way ANOVA and Student’s t test. A Kruskal-Wallis test followed by Bonferroni-corrected Mann-Whitney tests was performed if data did not pass the D’Agostino-Pearson normality test.ResultsLIF-treated rats showed significantly lower levels of the LIF receptor and interferon gamma in the spleen and CD11b levels in the brain compared to their PBS-treated counterparts. Fluorescence from isolectin-binding immune cells was more prominent in the ipsilateral cortex and striatum after PBS treatment compared to LIF treatment. MCAO + LIF significantly decreased splenic levels of CD11b and CD3 compared to sham surgery. MCAO + PBS treatment significantly elevated splenic levels of interferon inducible protein-10 at 72 h after MCAO, while LIF treatment after MCAO returned interferon inducible protein 10 to sham levels. LIF administration with interferon gamma + LPS significantly reduced the IL-12/IL-10 production ratio compared to macrophages treated with interferon gamma + LPS alone.ConclusionsThese data demonstrate that LIF promotes anti-inflammatory signaling through alterations of the IL-12/interferon gamma/interferon inducible protein 10 pathway.

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Association Between Splenic Contraction and the Systemic Inflammatory Response After Acute Ischemic Stroke Varies with Age and Race

Cited by 19 publications

References 45 publications

Systemic Inflammatory Response Syndrome and Outcomes in Ischemic Patients Treated with Endovascular Treatment

Systemic Inflammatory Response Syndrome and Outcomes in Ischemic Patients Treated with Endovascular Treatment

The splenic response to stroke: from rodents to stroke subjects

Leukemia inhibitory factor modulates the peripheral immune response in a rat model of emergent large vessel occlusion

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