scholarly journals Mechanisms and Therapeutic Targets of Depression After Intracerebral Hemorrhage

2018 ◽  
Vol 9 ◽  
Author(s):  
Yinan Wu ◽  
Liangliang Wang ◽  
Kaimin Hu ◽  
Chengcheng Yu ◽  
Yuanhan Zhu ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Therapeutic Targets

Neuroinflammation Mediated by NLRP3 Inflammasome After Intracerebral Hemorrhage and Potential Therapeutic Targets

2020 ◽  
Vol 57 (12) ◽  
pp. 5130-5149
Author(s):  
Linglong Xiao ◽  
Huaping Zheng ◽  
Jing Li ◽  
Qinghua Wang ◽  
Haitao Sun
Keyword(s):  
Intracerebral Hemorrhage ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Targets

scholarly journals WITHDRAWN: Mechanisms and potential therapeutic targets for intracerebral hemorrhage

2019 ◽  
Author(s):  
Wei Hua ◽  
Xiuli Yang ◽  
Xuemei Chen ◽  
Honglei Ren ◽  
Michael Hong ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Therapeutic Targets

scholarly journals Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Xin Hu ◽  
Chuanyuan Tao ◽  
Qi Gan ◽  
Jun Zheng ◽  
Hao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Damage ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Heme Iron ◽  
Mortality And Morbidity ◽  
Underlying Mechanisms ◽  
Damaging Effects

Intracerebral hemorrhage (ICH) is associated with the highest mortality and morbidity despite only constituting approximately 10–15% of all strokes. Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal blood are responsible for its highly damaging effects. Oxidative stress (OS) also plays an important role in brain injury after ICH but attracts less attention than other factors. Increasing evidence has demonstrated that the metabolite axis of hemoglobin-heme-iron is the key contributor to oxidative brain damage after ICH, although other factors, such as neuroinflammation and prooxidases, are involved. This review will discuss the sources, possible molecular mechanisms, and potential therapeutic targets of OS in ICH.

scholarly journals Mechanisms and potential therapeutic targets for spontaneous intracerebral hemorrhage

2020 ◽  
Vol 1 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Wei Hua ◽  
Xuemei Chen ◽  
Junmin Wang ◽  
Weidong Zang ◽  
Chao Jiang ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Therapeutic Targets ◽  
Spontaneous Intracerebral Hemorrhage

Abstract TP327: Major Inflammatory Pathways in Peripheral Blood Associate With Intracerebral Hemorrhage Volume in Human

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Marc Durocher ◽  
Bradley Ander ◽  
Alan Yee ◽  
Glen Jickling ◽  
Kwan Ng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intracerebral Hemorrhage ◽  
Peripheral Blood ◽  
Critical Role ◽  
Therapeutic Targets ◽  
Fc Receptor ◽  
Whole Genome ◽  
Blood Draw ◽  
Inflammatory Pathways ◽  
Pathway Activation

Objectives: Intracerebral hemorrhage (ICH) volume is a major determinant of functional outcome. The peripheral immune system plays a critical role in post-ICH damage and repair. Identifying potential modulators of ICH volume may guide the search for therapeutic targets. We performed a whole genome expression study in peripheral blood to examine the immune response following ICH with respect to ICH volume. Methods: Whole-genome RNA expression from 18 ICH subjects (14M/4F) was assessed on Affymetrix HTA 2.0 microarrays. Volumetric measurements were conducted on CT images using AnalyzePro. Multiple Regression including ICH volume while accounting for time from ICH onset to blood draw and interval between scan time and blood draw, was performed. A partial correlation between gene expression and ICH volume was calculated, with FDR p<0.3 (nominal p<0.005) and Pearson Correlation coefficient r>|0.6| considered significant. Pathway analysis and activation/suppression prediction of over-represented pathways was performed (Benjamini-Hochberg p<0.05, pathway activation/suppression Z-score >|2|). Results: Gene expression levels of 281 genes, including coding (mRNA) and non-coding RNA (i.e. several miRNAs) were associated with ICH volume. Major pathways, such as Neuroinflammation Signaling, were predicted to be activated in subjects with larger ICH volumes. So were Inflammasome Pathway, Toll-like Receptor, Leukocyte Extravasation, NF-kB signaling and FC? Receptor-Mediated Phagocytosis – some of which have been associated with poor clinical outcomes. Scavenger mechanisms, such as FC? Receptor-Mediated Phagocytosis, have been implicated in hematoma resolution. Thrombin Signaling, involved in coagulation, was also activated in subjects with larger ICH volumes. Peroxisome Proliferator-Activated Receptor (PPAR) Signaling was predicted to be suppressed in subjects with larger ICH volumes. PPAR pathway activation may have a neuroprotective effect following experimental ICH. Conclusions: We provide human data on genes and pathways associated with ICH volume. The results reveal major inflammatory pathways associated with ICH volume, which may be therapeutic targets for human ICH.

scholarly journals An Intersectional Study of LncRNAs and mRNAs Reveals the Potential Therapeutic Targets of Buyang Huanwu Decoction in Experimental Intracerebral Hemorrhage

2018 ◽  
Vol 46 (5) ◽  
pp. 2173-2186 ◽  
Author(s):  
Hanjin Cui ◽  
Tao Liu ◽  
Pengfei Li ◽  
Ali Yang ◽  
Huajun Zhou ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Oxygen Transport ◽  
Therapeutic Targets ◽  
Differentially Expressed ◽  
Positive Interactions ◽  
Pyruvate Metabolism ◽  
Buyang Huanwu Decoction ◽  
Highly Expressed Genes ◽  
Pathway Analyses ◽  
Upregulated Genes

Background/Aims: Both experimental and clinical studies have revealed satisfactory effects of the traditional Chinese formula Buyang Huanwu decoction (BYHWD) in improving post-intracerebral hemorrhage (ICH) neurological deficiencies. However, the multifaceted mechanisms of BYHWD in ICH treatment are not comprehensively understood. The present study explored various therapeutic targets of BYHWD by using lncRNA and mRNA transcriptomics. Methods: LncRNA and mRNA microarrays were used to identify differentially expressed genes. ICH-induced upregulated genes (ICH vs sham) and BYHWD-induced downregulated genes (BYHWD vs ICH) were first identified. The intersection between these 2 sets was determined to identify ICH-induced highly expressed genes that were reversed by BYHWD. Then, the genes downregulated after ICH and the genes upregulated after BYHWD treatment were used to generate another set of intersections. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were subsequently performed to determine relative biological functions and signaling transduction pathways according to genes within the intersections. Quantitative real-time PCR was used to validate changes in gene expression observed using the microarray. Finally, a lncRNA-mRNA co-expression network was established to identify links among the genes within the intersections. Results: A total of 18 differentially expressed lncRNAs and 33 differentially expressed mRNAs were identified using 2 lncRNA arrays (ICH vs sham and BYHWD vs ICH). The altered genes were enriched in the hemoglobin complex, oxygen transport and oxygen transporter and were closely associated with pyruvate metabolism. The co-expression network consisted of 53 nodes and 595 connections (308 positive interactions and 287 negative interactions). Conclusion: The hemoglobin complex, oxygen transport, oxygen transporter activity and pyruvate metabolism are possible therapeutic targets of BYHWD in ICH treatment. The present study provides the basis and direction for future investigations to explore the mechanisms by which BYHWD protects against long-term neurological deficiencies after ICH.

scholarly journals Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update

2020 ◽  
Vol 40 (9) ◽  
pp. 1752-1768 ◽  
Author(s):  
Honglei Ren ◽  
Ranran Han ◽  
Xuemei Chen ◽  
Xi Liu ◽  
Jieru Wan ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Recent Progress ◽  
Inflammatory Responses ◽  
Clinical Success ◽  
Therapeutic Targets ◽  
Secondary Brain Injury ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
Laboratory Technology ◽  
Made In

Intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality and disability but no specific or effective treatment. In the last two decades, much has been learned about the pathologic mechanisms of ICH. It is now known that after ICH onset, immune and inflammatory responses contribute to blood–brain barrier disruption, edema development, and cell death processes, jointly resulting in secondary brain injury. However, the translation of potential therapies from preclinical to clinical success has been disappointing. With the development of new laboratory technology, recent progress has been made in the understanding of ICH pathomechanisms, and promising therapeutic targets have been identified. This review provides an update of recent progress on ICH and describes the prospects for further preclinical studies in this field. Our goal is to discuss new therapeutic targets and directions for the treatment of ICH and promote the effective transformation from preclinical to clinical trials.

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