scholarly journals Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

2013 ◽  
Vol 34 (5) ◽  
pp. E9 ◽  
Author(s):  
Praveen K. Belur ◽  
Jason J. Chang ◽  
Shuhan He ◽  
Benjamin A. Emanuel ◽  
William J. Mack
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Mass Effect ◽  
Therapeutic Strategies ◽  
Experimental Models ◽  
Thrombin Inhibitors ◽  
Hematoma Expansion ◽  
Secondary Brain Injury ◽  
Limited Efficacy ◽  
Experimental Therapies

Intracerebral hemorrhage (ICH) is associated with a higher degree of morbidity and mortality than other stroke subtypes. Despite this burden, currently approved treatments have demonstrated limited efficacy. To date, therapeutic strategies have principally targeted hematoma expansion and resultant mass effect. However, secondary mechanisms of brain injury are believed to be critical effectors of cell death and neurological outcome following ICH. This article reviews the pathophysiology of secondary brain injury relevant to ICH, examines pertinent experimental models, and highlights emerging therapeutic strategies. Treatment paradigms discussed include thrombin inhibitors, deferoxamine, minocycline, statins, granulocyte-colony stimulating factors, and therapeutic hypothermia. Despite promising experimental and preliminary human data, further studies are warranted prior to effective clinical translation.

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage–induced secondary brain injury and as potential targets for intervention

2012 ◽  
Vol 32 (4) ◽  
pp. E8 ◽  
Author(s):  
Ranjith Babu ◽  
Jacob H. Bagley ◽  
Chunhui Di ◽  
Allan H. Friedman ◽  
Cory Adamson
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Mass Effect ◽  
Thrombin Inhibitors ◽  
Hematoma Expansion ◽  
Secondary Brain Injury ◽  
Antiinflammatory Drugs ◽  
Primary Hemorrhage

Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.

scholarly journals Mechanisms of Oxidative Stress and Therapeutic Targets following Intracerebral Hemorrhage

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zhenjia Yao ◽  
Qinqin Bai ◽  
Gaiqing Wang
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Intracerebral Hemorrhage ◽  
Blood Brain Barrier ◽  
Therapeutic Strategies ◽  
Secondary Brain Injury ◽  
Oxygen Species ◽  
Current State

Oxidative stress (OS) is induced by the accumulation of reactive oxygen species (ROS) following intracerebral hemorrhage (ICH) and plays an important role in secondary brain injury caused by the inflammatory response, apoptosis, autophagy, and blood-brain barrier (BBB) disruption. This review summarizes the current state of knowledge regarding the pathogenic mechanisms of brain injury after ICH, markers for detecting OS, and therapeutic strategies that target OS to mitigate brain injury.

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
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