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Ekkert A, Šliachtenko A, Utkus A, Jatužis D. Intracerebral Hemorrhage Genetics. Genes (Basel) 2022; 13:genes13071250. [PMID: 35886033 PMCID: PMC9322856 DOI: 10.3390/genes13071250] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 07/04/2022] [Accepted: 07/11/2022] [Indexed: 02/01/2023] Open
Abstract
Intracerebral hemorrhage (ICH) is a devastating type of stroke, frequently resulting in unfavorable functional outcomes. Up to 15% of stroke patients experience ICH and approximately half of those have a lethal outcome within a year. Considering the huge burden of ICH, timely prevention and optimized treatment strategies are particularly relevant. Nevertheless, ICH management options are quite limited, despite thorough research. More and more trials highlight the importance of the genetic component in the pathogenesis of ICH. Apart from distinct monogenic disorders of familial character, mostly occurring in younger subjects, there are numerous polygenic risk factors, such as hypertension, neurovascular inflammation, disorders of lipid metabolism and coagulation cascade, and small vessel disease. In this paper we describe gene-related ICH types and underlying mechanisms. We also briefly discuss the emerging treatment options and possible clinical relevance of the genetic findings in ICH management. Although existing data seems of more theoretical and scientific value so far, a growing body of evidence, combined with rapidly evolving experimental research, will probably serve clinicians in the future.
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Affiliation(s)
- Aleksandra Ekkert
- Center of Neurology, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania;
- Correspondence:
| | | | - Algirdas Utkus
- Center for Medical Genetics, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania;
| | - Dalius Jatužis
- Center of Neurology, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania;
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Singh N, Bansal Y, Bhandari R, Marwaha L, Singh R, Chopra K, Kuhad A. Resveratrol protects against ICV collagenase-induced neurobehavioral and biochemical deficits. JOURNAL OF INFLAMMATION-LONDON 2017; 14:14. [PMID: 28615993 PMCID: PMC5466723 DOI: 10.1186/s12950-017-0158-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 05/23/2017] [Indexed: 01/09/2023]
Abstract
Background Indeed, intracerebral hemorrhage (ICH) account for only 15% of all strokes but it is one of the most devastating subtype of stroke associated with behavioral, cognitive and neurological deficits. The primary cause of neurological deficits in ICH is the hematoma growth, generation of free radicals, inflammatory cytokines and exhausting endogenous anti-oxidant machinery. It has been found that neuroinflammation following ICH leads to exaggeration of hallmarks of ICH. With this background, the study was aimed to evaluate the protective effect of resveratrol (RSV) in intracerebroventricular (ICV) collagenase (COL) induced neurological deficits in rats. Methods The present study was designed to explore the protective effects of resveratrol (5, 10, 20 mg/kg) against ICV-COL induced ICH. Animals were subjected to a battery of behavioral tests to access behavioral changes, including neurological scoring tests (cylinder test, spontaneous motility, righting reflex, horizontal bar test, forelimb flexion), actophotometer, rotarod, Randall Sellito and von Frey. Post stroke depression was estimated using forced swim test (FST). Memory deficit was monitored using Morris water maze (MWM). Results Chronic treatment with RSV (20 mg/kg) for 21 days restored various behavioral changes, including neurological scoring tests (cylinder test, spontaneous motility, righting reflex, horizontal bar test, forelimb flexion), actophotometer, rotarod, Randall Sellito and Von Frey. RSV also restores increase in immobility time forced swim test used to evaluate post stroke depression and impaired memory deficit in Morris water maze. RSV administration also attenuated increased nitro-oxidative stress and TNF-α level. RSV being a potent antioxidant also restores changes in endogenous anti-oxidant levels. Conclusion In conclusion, our research demonstrates that RSV has a protective effect against ICH by virtue of its anti-inflammatory property and antioxidant and nitrosative stress restoring property.
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Affiliation(s)
- Navdeep Singh
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India
| | - Yashika Bansal
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India
| | - Ranjana Bhandari
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India
| | - Lovish Marwaha
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India
| | - Raghunath Singh
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India
| | - Kanwaljit Chopra
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India
| | - Anurag Kuhad
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India
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Zeng Y, Zhang L, Hu Z, Yang Q, Ma M, Liu B, Xia J, Xu H, Liu Y, Du X. 807C/T polymorphism of platelet glycoprotein Ia gene is associated with cerebral hemorrhage in a Chinese population. Int J Neurosci 2015; 126:729-33. [DOI: 10.3109/00207454.2015.1067891] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
China reports more patients with stroke than anywhere else in the world. While there is still a great deal of unknown information, stroke research has been making great progress in recent years. This study will review and discuss a variety of factors such as clinical research, population and genetic epidemiology, brain ischemia/reperfusion exploring, leukoencephalopathy (CADASIL), neural stem cell and stroke, neuroprotective treatment for stroke, clinical therapy test in stroke, rehabilitation and prevention. Cities and towns in China have good integrated systems for registering and investigating strokes. Chinese researchers have followed closely the international level of stroke treatment with a forward position in neural stem cell. Traditional Chinese drugs have featured effects on neuroprotective treatment for stroke which has also been investigated. Chinese scientists suggested a new way of dividing neuroprotectors in stroke. The clinical therapy test with urokinase and defibrase for cerebral infarction in China is effective and relatively safe, yet the original papers published by Chinese researchers and clinical effects for patient treatment still need to be improved and updated.
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Affiliation(s)
- Gangzhi Wei
- Department of Neurology, Xuanwu Hospital, the Capital University of Medical Sciences, Beijing 100053, China
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Fibrinogen polymorphisms associated with sporadic cerebral hemorrhage in a Chinese population. J Clin Neurosci 2012; 19:753-6. [PMID: 22386478 DOI: 10.1016/j.jocn.2011.09.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 08/25/2011] [Accepted: 09/23/2011] [Indexed: 11/23/2022]
Abstract
Fibrinogen plays an important role in the intrinsic and extrinsic pathways of blood coagulation. This study investigated the association between common variants in the fibrinogen gene and the risk of developing sporadic cerebral hemorrhage (CH). We performed genotyping analyses for three single nucleotide polymorphisms (SNP) in the fibrinogen gene in a case-controlled study involving 195 patients with CH and 116 control participants; both groups were of southern Han-Chinese origin. Logistic regression analysis indicated that haplotypes ATA (rs1800790+rs1800787+rs6050), AA (rs1800790+rs6050) and TA (rs1800787+rs6050) could nearly double the risk of sporadic CH (odds ratio [OR]=1.738, 95% confidence interval [CI]: 1.103-2.740, p=0.017; adjusted OR=1.762, 95% CI: 1.042-2.982, p=0.035), although the three SNP were not associated with sporadic CH when analyzed separately. These findings indicate that rs1800790, rs1800787 and rs6050 polymorphisms may contribute to the etiology of sporadic CH in the Chinese population.
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Abstract
Intracranial aneurysms (IAs) are the dilatations of blood vessels in the brain and pose potential risk of rupture leading to subarachnoid hemorrhage. Although the genetic basis of IAs is poorly understood, it is well-known that genetic factors play an important part in the pathogenesis of IAs. Therefore, the identifying susceptible genetic variants might lead to the understanding of the mechanism of formation and rupture of IAs and might also lead to the development of a pharmacological therapy. To elucidate the molecular pathogenesis of diseases has become a crucial step in the development of new treatment strategies. Although extensive genetic research and its potential implications for future prevention of this often fatal condition are urgently needed, efforts to elucidate the susceptibility loci of IAs are hindered by the issues bewildering the most common and complex genetic disorders, such as low penetrance, late onset, and uncertain modes of inheritance. These efforts are further complicated by the fact that many IA lesions remain asymptomatic or go undiagnosed. In this review, we present and discuss the current status of genetic studies of IAs and we recommend comprehensive genome-wide association studies to identify genetic loci that underlie this complex disease.
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Affiliation(s)
- Jun Zhang
- Department of Neurosurgery, The University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Richard E. Claterbuck
- Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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Banerjee I, Gupta V, Ganesh S. Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis. J Hum Genet 2006; 52:205-219. [PMID: 17171228 DOI: 10.1007/s10038-006-0098-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2006] [Accepted: 11/23/2006] [Indexed: 01/05/2023]
Abstract
Stroke is a heterogeneous multifactorial disease and is thought to have a polygenic basis. Case-control studies on gene sequence variations have identified a number of potential genetic predisposition factors, but due to the conflicting results, uncertainty remains on the effect of these polymorphisms on risk for the development of stroke. To qualitatively and quantitatively assess the risk associated with different gene polymorphisms for stroke in Asian populations, we comprehensively searched and identified all the studies of association. Clinically overt case-control studies were selected only if neuroimaging had been used as the confirmatory measure for diagnosis of stroke. We performed a meta-analysis of the three most investigated genes, viz., methylenetetrahydrofolate reductase (MTHFR), apolipoprotein E (ApoE) and angiotensin-converting enzyme (ACE). Statistically significant association with stroke were identified for C677T polymorphism of MTHFR [random effects odds ratio (OR) = 1.47, 95% confidence interval (95% CI) 1.19, 1.82; P = 0.0004] and marginally significant association was detected with allele epsilon 4 of ApoE (random effects OR = 1.47, 95% CI 1.00, 2.15; P = 0.049). The sensitivity analysis (exclusion of studies with controls not in Hardy-Weinberg equilibrium) revealed a significant association of stroke with the MTHFR C677T and ApoE epsilon 4 alleles but showed no association with ACE gene insertion/deletion polymorphism.
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Affiliation(s)
- Indranil Banerjee
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, 208016, India
| | - Veena Gupta
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, 208016, India
| | - Subramaniam Ganesh
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, 208016, India.
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Ponsuksili S, Murani E, Schellander K, Schwerin M, Wimmers K. Identification of functional candidate genes for body composition by expression analyses and evidencing impact by association analysis and mapping. ACTA ACUST UNITED AC 2005; 1730:31-40. [PMID: 16005530 DOI: 10.1016/j.bbaexp.2005.06.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2005] [Revised: 05/27/2005] [Accepted: 06/02/2005] [Indexed: 11/28/2022]
Abstract
This study aims to identify hepatic genes affecting traits related to muscularity and obesity by combining expression analyses, association studies, and gene mapping. Functional candidate genes with trait-associated expression were obtained by hybridising custom made application-specific cDNA microarrays with targets of discordant sib pairs of a porcine experimental population. Out of 238 genes addressed, nine genes were regulated by the factor>or=2 between the sib pairs. Differential gene expression was independently confirmed for selected genes by real time RT-PCR. Transcript levels of four genes (APOH, PEDF, SLCO1B3, TBG) were significantly different between the phenotype groups. Screening for trait associated markers within TBG and APOH by comparative sequencing of discordant sib pairs revealed a SNP at position nt 778 (A>C) (N229H) of TBG. No polymorphism in APOH was detected. Association analysis confirmed effects of TBG on carcass traits statistically. Allocating TBG to a QTL region on chromosome X revealed genetic evidence for the effect. Moreover, our results indicate that there are probably two polymorphisms segregating-one (N229H) altering binding capability of TBG and another still to be detected altering the transcription rate of TBG.
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Affiliation(s)
- Siriluck Ponsuksili
- Institute of Animal Breeding and Genetics, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany; Research Institute for the Biology of Farm Animals, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
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Ouchi M, West K, Crabb JW, Kinoshita S, Kamei M. Proteomic analysis of vitreous from diabetic macular edema. Exp Eye Res 2005; 81:176-82. [PMID: 16080911 DOI: 10.1016/j.exer.2005.01.020] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2004] [Revised: 01/13/2005] [Accepted: 01/24/2005] [Indexed: 01/28/2023]
Abstract
To identify and analyze diabetic macular edema (DME)-related proteins in the vitreous, en masse, using two-dimensional gel (2D gel) electrophoresis and mass-spectrometry (MS). Vitreous samples were corrected from 20 eyes with pre-proliferative diabetic retinopathy associated with DME (DME group) and without DME (non-DME group). They were subjected to 2D gel electrophoresis, and the spot intensities were compared between the groups. Apparently visible spots were excised from the gel, and the proteins were identified by liquid chromatography tandem MS (LC MS/MS) sequence analysis. We identified 14 proteins from the DME group, and 15 proteins from the non-DME group. The intensity of eight spots was markedly higher in DME than non-DME samples and one spot was detected only in non-DME samples. From the eight spots, six proteins were identified, including PEDF, ApoA-4, ApoA-1, Trip-11, PRBP, and VDBP. On the other hand, Apo H was expressed only in non-DME. Certain vitreous proteins expressed exclusively in DME and lacked in DME. These chemical mediators in the posterior vitreous may play a role in the pathogenesis of DME.
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Affiliation(s)
- Masayuki Ouchi
- Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji Kamigyo-ku, Kyoto 602-0841, Kyoto, Japan
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Bai GQ, Liu Y, Cheng J, Zhang SL, Yue YF, Huang YP, Zhang LY. Transactivating effect of complete S protein of hepatitis B virus and cloning of genes transactivated by complete S protein using suppression subtractive hybridization technique. World J Gastroenterol 2005; 11:3893-8. [PMID: 15991289 PMCID: PMC4504892 DOI: 10.3748/wjg.v11.i25.3893] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the transactivating effect of complete S protein of hepatitis B virus (HBV) and to construct a subtractive cDNA library of genes transactivated by complete S protein of HBV by suppression subtractive hybridization (SSH) technique and to clone genes associated with its transactivation activity, and to pave the way for elucidating the pathogenesis of hepatitis B virus infection.
METHODS: pcDNA3.1(-)-complete S containing full-length HBV S gene was constructed by insertion of HBV complete S gene into BamH I/Kpn I sites. HepG2 cells were cotransfected with pcDNA3.1(-)-complete S and pSV-lacZ. After 48 h, cells were collected and detected for the expression of β-galactosidase (β-gal). Suppression subtractive hybridization and bioinformatics techniques were used. The mRNA of HepG2 cells transfected with pcDNA3.1(-)-complete S and pcDNA3.1(-) empty vector was isolated, and detected for the expression of complete S protein by reverse transcription polymerase chain reaction (RT-PCR) method, and cDNA was synthesized. After digestion with restriction enzyme RsaI, cDNA fragments were obtained. Tester cDNA was then divided into two groups and ligated to the specific adaptors 1 and 2, respectively. After tester cDNA had been hybridized with driver cDNA twice and underwent nested PCR twice, amplified cDNA fragments were subcloned into pGEM-Teasy vectors to set up the subtractive library. Amplification of the library was carried out within E. coli strain DH5α. The cDNA was sequenced and analyzed in GenBank with BLAST search after polymerase chain reaction (PCR) amplification.
RESULTS: The complete S mRNA could be detected by RT-PCR in HepG2 cells transfected with the pcDNA3.1(-)-complete S. The activity of β-gal in HepG2 cells transfected with the pcDNA3.1(-)-complete S was 6.9 times higher than that of control plasmid. The subtractive library of genes transactivated by HBV complete S protein was constructed successfully. The amplified library contains 86 positive clones. Colony PCR showed that 86 clones contained DNA inserts of 200-1 000 bp, respectively. Sequence analysis was performed in 35 clones randomly, and the full length sequences were obtained with bioinformatics method and searched for homologous DNA sequence from GenBank, altogether 33 coding sequences were obtained. These cDNA sequences might be target genes transactivated by complete S protein of HBV. Moreover, two unknown genes were discovered, full length coding sequences were obtained by bioinformatics techniques, one of them was named complete S transactivated protein 1 (CSTP1) and registered in GenBank (AY553877).
CONCLUSION: The complete S gene of HBV has a transactivating effect on SV40 early promoter. A subtractive cDNA library of genes transactivated by HBV complete S protein using SSH technique has been constructed successfully. The obtained sequences may be target genes transactivated by HBV complete S protein among which some genes coding proteins are involved in cell cycle regulation, metabolism, immunity, signal transduction, cell apoptosis and formation mechanism of hepatic carcinoma.
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Affiliation(s)
- Gui-Qin Bai
- Department of Obstetrics and Gynecology of First Hospital, Xi'an Jiaotong University, Jiankang Road 1, Xi'an 710061, Shaanxi Province, China
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N/A. N/A. Shijie Huaren Xiaohua Zazhi 2004; 12:2463-2466. [DOI: 10.11569/wcjd.v12.i10.2463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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