The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistan...The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA ＋ AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Hart population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.展开更多
Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by ...Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage.The mechanisms underlying exacerbated hemorrhage are not fully understood.This study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical thrombectomy.The results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+mice.This indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after reperfusion.This observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic stroke.Endoplasmic reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic conditions.In conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformation.Thus,suppression of the VEGF pathway could be a potential approach to allow reperfusion therapy in patients with diabetic stroke beyond the current treatment window.Experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong[CULATR 3834-15(approval date January 5,2016);3977-16(approval date April 13,2016);and 4666-18(approval date March 29,2018)].展开更多
Acute ischemic stroke(AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis(IVT) with...Acute ischemic stroke(AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis(IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, butkey limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy.展开更多
Stroke is a devastating and disabling cerebrovascular disease with some amount of residual deficit leading onto economic loss. Recent Indian studies have shown a stroke prevalence rate of 471.58/100,000 population. Th...Stroke is a devastating and disabling cerebrovascular disease with some amount of residual deficit leading onto economic loss. Recent Indian studies have shown a stroke prevalence rate of 471.58/100,000 population. This study was undertaken to analyse the clinical profile and to arrive at important factors contributing to stroke in 45 years group. This is a descriptive, retrospective cross—sectional study carried out on acute CVA patients, admitted to the I.I.M., RGGGH, Chennai. 150 patients were studied over a period of 3 months in the 2011. 20% of /= 45 years constituted our study population. 18.4% and 22.2% of males and females respectively were young stroke patients. Only 33.3% of patients were brought to the hospital within 6 hours. 90% patients had mild GCS score (>/=13/15) and presented with hemiplegia 76% and 18% had infarct and intracerebral hemorrhage(ICH) respectively. Risk factors: Type A personality (70.7%), Tobacco (60.7%) and Alcohol (44.7%) abuse, Systemic Hypertension (60.7%), Diabetes Mellitus (33.3%), Cardiac disorders (14%). Stroke was seen to be more common in >45 years but still young stroke carries paramount importance due to loss of productive years in these patients. Female predominance was seen in young stroke, with particular reference to puerperal period. Among the comorbid illness systemic hypertension followed by cardiac disorders had important contributing role in young strokes. Most of the patients with infarct and ICH were tobacco and alcohol abusers respectively. A holistic approach encompassing further research in factors involved in young stroke, public awareness, behavioural modification and comorbid medical illness management is the need for the hour.展开更多
文摘The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA ＋ AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Hart population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.
基金supported by Health and Medical Research Fund,the Food and Health Bureau,The Government of the Hong Kong Special Administrative Region(03142256)General Research Fund,Hong Kong Research Grants Council(GRF#HKU773613M)+1 种基金Seed Funding Programme for Basic Research(201811159123,201910159191)The University of Hong Kong(all to ACYL)。
文摘Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage.The mechanisms underlying exacerbated hemorrhage are not fully understood.This study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical thrombectomy.The results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+mice.This indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after reperfusion.This observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic stroke.Endoplasmic reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic conditions.In conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformation.Thus,suppression of the VEGF pathway could be a potential approach to allow reperfusion therapy in patients with diabetic stroke beyond the current treatment window.Experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong[CULATR 3834-15(approval date January 5,2016);3977-16(approval date April 13,2016);and 4666-18(approval date March 29,2018)].
文摘Acute ischemic stroke(AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis(IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, butkey limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy.
文摘Stroke is a devastating and disabling cerebrovascular disease with some amount of residual deficit leading onto economic loss. Recent Indian studies have shown a stroke prevalence rate of 471.58/100,000 population. This study was undertaken to analyse the clinical profile and to arrive at important factors contributing to stroke in 45 years group. This is a descriptive, retrospective cross—sectional study carried out on acute CVA patients, admitted to the I.I.M., RGGGH, Chennai. 150 patients were studied over a period of 3 months in the 2011. 20% of /= 45 years constituted our study population. 18.4% and 22.2% of males and females respectively were young stroke patients. Only 33.3% of patients were brought to the hospital within 6 hours. 90% patients had mild GCS score (>/=13/15) and presented with hemiplegia 76% and 18% had infarct and intracerebral hemorrhage(ICH) respectively. Risk factors: Type A personality (70.7%), Tobacco (60.7%) and Alcohol (44.7%) abuse, Systemic Hypertension (60.7%), Diabetes Mellitus (33.3%), Cardiac disorders (14%). Stroke was seen to be more common in >45 years but still young stroke carries paramount importance due to loss of productive years in these patients. Female predominance was seen in young stroke, with particular reference to puerperal period. Among the comorbid illness systemic hypertension followed by cardiac disorders had important contributing role in young strokes. Most of the patients with infarct and ICH were tobacco and alcohol abusers respectively. A holistic approach encompassing further research in factors involved in young stroke, public awareness, behavioural modification and comorbid medical illness management is the need for the hour.
