High plasma complement C4 levels as a novel predictor of clinical outcome in intracerebral hemorrhage

Wu, Moxin; Chen, Kai; Jiang, Min; Xie, Fusheng; Cao, Xin; Chen, Liang; Chen, Zhiying; Yin, Xiaoping

doi:10.3389/fnagi.2023.1103278

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…The inclusion and exclusion criteria have been previously described. 25 Peripheral blood samples were centrifuged at 3000 g for 10 min, separated and immediately preserved at −80°C for subsequent analysis. Written informed consent was obtained from the patients or their relatives and the control individuals, and the study was approved by the Medical Ethics Committee of the Affiliated Hospital of Jiujiang University (Grant No.…”

Section: Methodsmentioning

confidence: 99%

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Normobaric hyperoxia alleviates complement C3‐mediated synaptic pruning and brain injury after intracerebral hemorrhage

Wu,

Chen,

Zhao

et al. 2024

CNS Neurosci Ther

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BackgroundIntracerebral hemorrhage (ICH) is a common cerebrovascular disease, and the complement cascade exacerbates brain injury after ICH. As the most abundant component of the complement system, complement component 3 (C3) plays essential roles in all three complement pathways. However, the effects of C3 on neurological impairment and brain injury in ICH patients and the related mechanism have not been fully elucidated. Normobaric hyperoxia (NBO) is regarded as a treatment for ICH patients, and recent clinical studies also have confirmed the neuroprotective role of NBO against acute ICH‐mediated brain damage, but the underlying mechanism still remains elusive.AimsIn the present study, we investigated the effects of complement C3 on NBO‐treated ICH patients and model mice, and the underlying mechanism of NBO therapy in ICH‐mediated brain injury.ResultsHemorrhagic injury resulted in the high plasma C3 levels in ICH patients, and the plasma C3 levels were closely related to hemorrhagic severity and clinical outcomes after ICH. BO treatment alleviated neurologic impairments and rescued the hemorrhagic‐induced increase in plasma C3 levels in ICH patients and model mice. Moreover, the results indicated that NBO exerted its protective effects of on brain injury after ICH by downregulating the expression of C3 in microglia and alleviating microglia‐mediated synaptic pruning.ConclusionsOur results revealed that NBO exerts its neuroprotective effects by reducing C3‐mediated synaptic pruning, which suggested that NBO therapy could be used for the clinical treatment of ICH.

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Section: Methodsmentioning

confidence: 99%

“…The matched healthy controls were selected from patients that visited our medical examination center between January 2022 and May 2022. The inclusion and exclusion criteria have been previously described 25 . Peripheral blood samples were centrifuged at 3000 g for 10 min, separated and immediately preserved at −80°C for subsequent analysis.…”

Section: Methodsmentioning

confidence: 99%

Normobaric hyperoxia alleviates complement C3‐mediated synaptic pruning and brain injury after intracerebral hemorrhage

Wu,

Chen,

Zhao

et al. 2024

CNS Neurosci Ther

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“…Level of plasma complement C4 was determined by turbidimetric measurements using complement C4 assay kit (No. 20230712, Kehua Bio-engineering Co., Ltd., Shanghai, China) ( 15 ). According to the manufacturer’s instructions, the lower C4 quantification limit was 0.16 g/L.…”

Section: Methodsmentioning

confidence: 99%

Association of plasma MMP-2 levels and prognosis of patients with intracerebral hemorrhage: a prospective cohort study

Yu,

Peng,

Chen

et al. 2023

Front. Neurol.

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ObjectiveThe role of MMP-2 in patients with ICH is controversial and the impact of plasma MMP-2 level on clinical outcome is still unclear.Materials and methodsIn this study, the peripheral venous blood was acquired from 93 patients with ICH and 88 healthy controls within 24 h of hospitalization and at enrollment. We retrospectively investigated plasma MMP-2 levels of patients and healthy controls. The edema volume, the NIHSS score, the GCS score, and mRS were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma MMP-2 levels with clinical outcomes. In addition, the plasma MMP-14 levels and complement C4 level were tested to explore the relationship with plasma MMP-2 level.ResultsThere was a significant reduction of plasma MMP-2 levels in ICH patients than that in healthy controls (38.02 ± 1.71 vs. 54.03 ± 2.15, p < 0.0001), and MMP-2 is negatively correlated with the edema volume (r = −0.2187, p < 0.05), NIHSS score (r = −0.2194, p < 0.05), blood leucocyte count (r = −0.2549, p = 0.012), and complement C4 level (r = −0.2723, p = 0.005). There is positive correlation between MMP-2 level and GCS score (r = 0.2451, p = 0.01) and MMP-14 level (r = 0.7013, p = 0.005). The multivariate analysis revealed that reduced plasma MMP-2 level is associated with elevated edema volume (OR = 0.2604, 95% CI [0.07 to 0.84], p = 0.02).ConclusionThe plasma MMP-2 level in patients with ICH is significantly lower than that of healthy controls, and plasma MMP-2 level may be a prognostic factor. Plasma MMP-2 levels are correlated with the clinical outcomes of patients and negatively correlated with blood leucocyte count and complement C4 level in patients with ICH.

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“…In addition, plasma C4 levels are significantly elevated and are associated with clinical outcomes in patients with hemorrhagic stroke. 82 More importantly, C4 is critical for synaptic pruning, and variations in C4 induce excessive neuronal complement deposition and contribute to increased microglial synapse uptake in cocultured human iPSC-derived neurons and microglia. 83 Two studies involving mouse models also revealed that overexpression of the schizophrenia-associated gene C4 promotes excessive synaptic loss and behavioral changes through microglial synaptic engulfment.…”

Section: Complement Systemmentioning

confidence: 99%

“…Normobaric hyperoxia therapy exerts neuroprotective effects by reducing C3‐mediated synaptic pruning in ICH patients and in a collagenase‐induced mouse model. In addition, plasma C4 levels are significantly elevated and are associated with clinical outcomes in patients with hemorrhagic stroke 82 . More importantly, C4 is critical for synaptic pruning, and variations in C4 induce excessive neuronal complement deposition and contribute to increased microglial synapse uptake in cocultured human iPSC‐derived neurons and microglia 83 .…”

Section: Synapse‐related Signaling Pathways In Strokementioning

confidence: 99%

Current evidence of synaptic dysfunction after stroke: Cellular and molecular mechanisms

Li,

Jiang,

Fang

et al. 2024

CNS Neurosci Ther

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BackgroundStroke is an acute cerebrovascular disease in which brain tissue is damaged due to sudden obstruction of blood flow to the brain or the rupture of blood vessels in the brain, which can prompt ischemic or hemorrhagic stroke. After stroke onset, ischemia, hypoxia, infiltration of blood components into the brain parenchyma, and lysed cell fragments, among other factors, invariably increase blood–brain barrier (BBB) permeability, the inflammatory response, and brain edema. These changes lead to neuronal cell death and synaptic dysfunction, the latter of which poses a significant challenge to stroke treatment.ResultsSynaptic dysfunction occurs in various ways after stroke and includes the following: damage to neuronal structures, accumulation of pathologic proteins in the cell body, decreased fluidity and release of synaptic vesicles, disruption of mitochondrial transport in synapses, activation of synaptic phagocytosis by microglia/macrophages and astrocytes, and a reduction in synapse formation.ConclusionsThis review summarizes the cellular and molecular mechanisms related to synapses and the protective effects of drugs or compounds and rehabilitation therapy on synapses in stroke according to recent research. Such an exploration will help to elucidate the relationship between stroke and synaptic damage and provide new insights into protecting synapses and restoring neurologic function.

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High plasma complement C4 levels as a novel predictor of clinical outcome in intracerebral hemorrhage

Cited by 5 publications

References 39 publications

Normobaric hyperoxia alleviates complement C3‐mediated synaptic pruning and brain injury after intracerebral hemorrhage

Normobaric hyperoxia alleviates complement C3‐mediated synaptic pruning and brain injury after intracerebral hemorrhage

Association of plasma MMP-2 levels and prognosis of patients with intracerebral hemorrhage: a prospective cohort study

Current evidence of synaptic dysfunction after stroke: Cellular and molecular mechanisms

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