Hemorrhage-Induced Sphingosine Kinase 1 Contributes to Ferroptosis-Mediated Secondary Brain Injury in Intracerebral Hemorrhage

2022 ◽  
Author(s):  
Xiaojun Diao ◽  
Qi Cui ◽  
Ning Tian ◽  
Zixian Zhou ◽  
Wenjing Xiang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Sphingosine Kinase ◽  
Secondary Brain Injury ◽  
Sphingosine Kinase 1

scholarly journals Mitochondria: Novel Mechanisms and Therapeutic Targets for Secondary Brain Injury After Intracerebral Hemorrhage

2021 ◽  
Vol 12 ◽  
Author(s):  
Weixiang Chen ◽  
Chao Guo ◽  
Hua Feng ◽  
Yujie Chen
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Hemorrhagic Stroke ◽  
Secondary Brain Injury ◽  
Valuable Insight ◽  
Potential Therapeutic Target ◽  
Pathological Mechanism ◽  
Clinical Strategies ◽  
Inflammatory Activation ◽  
Insight Into

Intracerebral hemorrhage (ICH) is a destructive form of stroke that often results in death or disability. However, the survivors usually experience sequelae of neurological impairments and psychiatric disorders, which affect their daily functionality and working capacity. The recent MISTIE III and STICH II trials have confirmed that early surgical clearance of hematomas does not improve the prognosis of survivors of ICH, so it is vital to find the intervention target of secondary brain injury (SBI) after ICH. Mitochondrial dysfunction, which may be induced by oxidative stress, neuroinflammation, and autophagy, among others, is considered to be a novel pathological mechanism of ICH. Moreover, mitochondria play an important role in promoting neuronal survival and improving neurological function after a hemorrhagic stroke. This review summarizes the mitochondrial mechanism involved in cell death, reactive oxygen species (ROS) production, inflammatory activation, blood–brain barrier (BBB) disruption, and brain edema underlying ICH. We emphasize the potential of mitochondrial protection as a potential therapeutic target for SBI after stroke and provide valuable insight into clinical strategies.

RAB7L1 Participates in Secondary Brain Injury Induced by Experimental Intracerebral Hemorrhage in Rats

2020 ◽  
Vol 71 (1) ◽  
pp. 9-18
Author(s):  
Xiaoxing Tan ◽  
Yuchong Wei ◽  
Jie Cao ◽  
Degang Wu ◽  
Niansheng Lai ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Secondary Brain Injury

scholarly journals Rbfox-1 contributes to CaMKIIα expression and intracerebral hemorrhage-induced secondary brain injury via blocking micro-RNA-124

2020 ◽  
pp. 0271678X2091686 ◽  
Author(s):  
Fang Shen ◽  
Xiang Xu ◽  
Zhengquan Yu ◽  
Haiying Li ◽  
Haitao Shen ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Protein Level ◽  
Rna Binding ◽  
Neuronal Degeneration ◽  
Binding Protein ◽  
Neurological Diseases ◽  
Rna Binding Protein ◽  
Micro Rna ◽  
Secondary Brain Injury

RNA-binding protein fox-1 homolog 1 (Rbfox-1), an RNA-binding protein in neurons, is thought to be associated with many neurological diseases. To date, the mechanism on which Rbfox-1 worsens secondary cell death in ICH remains poorly understood. In this study, we aimed to explore the role of Rbfox-1 in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and to identify its underlying mechanisms. We found that the expression of Rbfox-1 in neurons was significantly increased after ICH, which was accompanied by increases in the binding of Rbfox-1 to Ca2+/calmodulin-dependent protein kinase II (CaMKIIα) mRNA and the protein level of CaMKIIα. In addition, when exposed to exogenous upregulation or downregulation of Rbfox-1, the protein level of CaMKIIα showed a concomitant trend in brain tissue, which further suggested that CaMKIIα is a downstream-target protein of Rbfox-1. The upregulation of both proteins caused intracellular-Ca2+ overload and neuronal degeneration, which exacerbated brain damage. Furthermore, we found that Rbfox-1 promoted the expression of CaMKIIα via blocking the binding of micro-RNA-124 to CaMKIIα mRNA. Thus, Rbfox-1 is expected to be a promising therapeutic target for SBI after ICH.

Inhibition of EPAC2 Attenuates Intracerebral Hemorrhage-Induced Secondary Brain Injury via the p38/BIM/Caspase-3 Pathway

2019 ◽  
Vol 67 (3) ◽  
pp. 353-363 ◽  
Author(s):  
Yan Zhuang ◽  
Hui Xu ◽  
Seidu A. Richard ◽  
Jie Cao ◽  
Haiying Li ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Caspase 3 ◽  
Secondary Brain Injury

Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage

2019 ◽  
Vol 178 ◽  
pp. 101610 ◽  
Author(s):  
Huimin Zhu ◽  
Zhiqiang Wang ◽  
Jixu Yu ◽  
Xiuli Yang ◽  
Feng He ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Secondary Brain Injury

scholarly journals Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression

2016 ◽  
Vol 37 (5) ◽  
pp. 1871-1882 ◽  
Author(s):  
Raimund Helbok ◽  
Alois Josef Schiefecker ◽  
Christian Friberg ◽  
Ronny Beer ◽  
Mario Kofler ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Electrode Placement ◽  
Secondary Brain Injury ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Strip Electrode ◽  
Hematoma Evacuation ◽  
Perihematomal Edema ◽  
Pathophysiologic Mechanisms

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3–5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9–22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

scholarly journals The Influence of Oxidative Stress on Neurological Outcomes in Spontaneous Intracerebral Hemorrhage

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1615
Author(s):  
Julia Masomi-Bornwasser ◽  
Elena Kurz ◽  
Christina Frenz ◽  
Jan Schmitt ◽  
Dominik M. A. Wesp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Total Antioxidant Status ◽  
Secondary Brain Injury ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Neurological Outcomes ◽  
Total Antioxidant ◽  
Patient’S Outcome ◽  
The Impact

Spontaneous intracerebral hemorrhage (ICH) causes, besides the primary brain injury, a secondary brain injury (SBI), which is induced, amongst other things, by oxidative stress (OS) and inflammation, determining the patient’s outcome. This study aims to assess the impact of OS in plasma and cerebrospinal fluid (CSF) on clinical outcomes in patients with ICH. A total of 19 ICH (volume > 30 cc) patients and 29 control patients were included. From day one until seven, blood and CSF samples were obtained, and ICH volume was calculated. OS markers, like malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-sulfhydryl (GSH), and the total antioxidant status (TAS) were measured. Clinical data on treatment and outcome were determined. Patients with mRS ≤ 4 showed significantly elevated SOD and GSH-Px levels in plasma compared to patients with poor CO (p = 0.004; p = 0.002). Initial increased TAS in plasma and increased MDA in CSF were linked to an unfavorable outcome after six months (p = 0.06, r = 0.45; p = 0.05, r = 0.44). A higher ICH volume was associated with a worse outcome at week six (p = 0.04, r = 0.47). OS plays a significant role in SBI. Larger ICHs, elevated MDA in CSF, and TAS in plasma were associated with a detrimental outcome, whereas higher plasma-SOD and -GSH-Px were associated with a favorable outcome.

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