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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major goal of the second International Workshop on "Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins: Application to Neurological Disorders" was the identification of important future research areas that would lead to accelerated and systematic progress in the field. Major themes identified for future research include the following: (1) Rigorous research protocols for fatty acid (FA) studies should be established to overcome errors introduced by small differences in chain length and degree of unsaturation. (2) Using cellular integration models consisting of endothelial cells, astrocytes, and neurons, investigation of functional lipidomics, cell-specific signaling by lipids, and nutritional considerations should be undertaken. (3) Educational programs should be undertaken for women of childbearing age on the health benefits of omega3 long chain (LC) polyunsaturated fatty acids (PUFA) from fish consumption vs risks of mercury in fish. (4) Studies of the "flip-flop" model of passive diffusion should be extended to include other quantitative measures, such as the sizes of different fatty acid pools. (5) Investigations to establish physiologic roles and concentrations of omega3 LC-PUFA in various compartments of the brain should be undertaken. (6) Further studies should be carried out to illuminate the role and behavior of tight junctions in the microvascular endothelium of the blood-brain barrier and astrocytes, with emphasis on developing new LC-PUFA and lipid-based carriers of biomolecules across this barrier. (7) Roles and localization of very low density lipoproteins, low density lipoprotein (LDL), and the LDL receptor in the brain and their interactions with omega3 LC-PUFA, cholesterol, apolipoprotein E1-4, and their derivatives in Alzheimer's disease (AD) should be assessed. (8) Investigation of intraneuronal synthesis of DHA and its effects on signal transduction, apoptosis, and neurite growth stimulation should be undertaken. (9) Nutrition-based behavioral affects of EPA and DHA, particularly with respect to the omega6:omega3 FA ratio, gene regulation, neurodevelopment, and conversion to bioactive molecules by cyclooxygenases (COX) and lipoxygenase, should be explored. (10) Further assessment of brain lipid metabolism and neurodevelopment should be performed in DHA-deficient rodent models, including the use of imaging techniques. (11) Potential toxic effects of COX overexpression and the possible consequences of DHA over-supplementation in various neurological and neurodevelopmental disorders should be characterized. (12) The relationship between LC-PUFA, stroke, and AD should be clarified, and neurogenetic metabolic diseases that could benefit from supplementation with omega3 LC-PUFA such as DHA should be identified.
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PMID:Brain uptake and utilization of fatty acids, lipids & lipoproteins: recommendations for future research. 1790 59

Cardiovascular diseases are major causes of mortality and disease in the Indian subcontinent, causing more than 25% of deaths. It has been predicted that these diseases will increase rapidly in India and this country will be host to more than half the cases of heart disease in the world within the next 15 years. Coronary heart disease and stroke have increased in both urban and rural areas. Case-control studies indicate that tobacco use, obesity with high waist:hip ratio, high blood pressure, high LDL cholesterol, low HDL cholesterol, abnormal apolipoprotein A-1:B ratio, diabetes, low consumption of fruits and vegetables, sedentary lifestyles and psychosocial stress are important determinants of cardiovascular diseases in India. These risk factors have increased substantially over the past 50 years and to control further escalation it is important to prevent them. National interventions such as increasing tobacco taxes, labelling unhealthy foods and trans fats, reduction of salt in processed foods and better urban design to promote physical activity may have a wide short-term impact.
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PMID:Epidemiology and causation of coronary heart disease and stroke in India. 1808 49

ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid peroxidation and oxLDL (oxidized low-density lipoprotein) formation. Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an increased risk of thrombotic events, as well as in ACS (acute coronary syndrome). OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs exist in other prothrombotic conditions, such as APE (acute pulmonary embolism) and stroke, has not been studied and their potential association with oxLDL and PON-1 activity is not known. In the present study, we determined prospectively the prevalence of anti-(apoA-1) IgG in patients with ACS (n=127), APE (n=58) and stroke (n=34), and, when present, we tested their association with oxLDL levels. The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control group and 0% in the APE and stroke groups. The ACS group had significantly higher median anti-(apoA-1) IgG titres than the other groups of patients. Patients with ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values than those who tested negative (226.5 compared with 47.7 units/l; P<0.00001) and controls. The Spearman ranked test revealed a significant correlation between anti-(apoA-1) IgG titres and serum oxLDL levels (r=0.28, P<0.05). No association was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or APE. In ACS, their presence is associated with higher levels of oxLDL and is directly proportional to the serum concentration of oxLDL. These results emphasize the role of humoral autoimmunity as a mediator of inflammation and coronary atherogenesis.
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PMID:Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low-density lipoprotein in acute coronary syndrome. 1808 36

In an elderly pool of 3288 subjects (65-84 years of age), taking part in the Italian Longitudinal Studies on Aging (ILSA). We evaluated the prevalence of acute myocardial infarction (AMI), the stroke, the non-fatal AMI+stroke cases in relation to the larger or smaller values of the apolipoprotein-B (Apo-B) level considered as cutoff point of normality (150 mg/100 ml). In addition, during the follow-up of 3 years, we observed the prevalence of all these pathologies (AMI, stroke, non-fatal AMI+stroke) in the subjects who had none of these syndromes at the start of the study period. At last, we studied the percentual occurrence of the parameters indicated by the IDF as signs of the metabolic syndrome (MS), and compared them between the subjects displaying higher or lower values of Apo-B of the normal level. Our results revealed that the Apo-B value may be considered as a predictive factor of lipidemic, atherogenic alterations, and it merits in this sense to be included in the diagnostic criteria of MS. However, it cannot be considered as an independent factor of preventive diagnosis of the non-fatal cardio-cerebrovascular complications.
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PMID:The significance of apolipoprotein-B (Apo-B) in the elderly as a predictive factor of cardio-cerebrovascular complications. 1870 Nov 71

Previous studies show that APOE *4 carriers are at increased risk for ischemic stroke and intracerebral hemorrhage (ICH). The APOE *4 gene is also linked to increased incidence of cerebral amyloid angiopathy. It has been suggested that apolipoprotein E4 expression leads to increased vascular amyloid deposition, which may explain the increased incidence of ICH in APOE *4 carriers. Here we show a significant increase in ICH in apoE4 targeted replacement mice compared with apoE3 mice. In all, 89% of the vessels in the apoE4 mice that showed evidence for hemorrhage contained fibrillar amyloid beta based on thioflavine-S staining. Aged apoE4 mice contained predominantly vascular amyloid deposits in the frontal cortex and hippocampus, but also showed evidence for parenchymal amyloid deposits. Most of the parenchymal amyloid appeared diffuse in nature; however, a small fraction was thioflavine-S positive, indicating presence of fibrillar amyloid. Electron microscopy further revealed evidence for fibrillar deposits in the vessel walls of apoE4 mice, but not apoE3 mice. The apoE4 targeted replacement mice do not harbor any mutation in the amyloid precursor protein gene and, therefore, are similar to the majority of humans susceptible to cerebral amyloid angiopathy and ICH, where the APOE genetic polymorphism is the only known genetic risk factor.
J Stroke Cerebrovasc Dis 2008 Sep
PMID:Human apolipoprotein E4 targeted replacement mice show increased prevalence of intracerebral hemorrhage associated with vascular amyloid deposition. 1875 11

Although smoking and hypertension are classic risk factors for atherothrombotic diseases, the relationship of dyslipidemia and vascular diseases, other than myocardial infarction, is less clearly established, especially in young subjects. In the current study, a detailed analysis of the lipid and apolipoprotein profiles was conducted in young patients of ischemic cerebral stroke (IS) and peripheral arterial disease (PAD). Plasma levels of C-reactive protein (hs-CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), and apolipoproteins A-I (ApoA-I) and apolipoproteins B (ApoB), which include the ApoB/ApoA-I ratio, were analyzed in a group of 81 patients who presented with IS (n = 46) or PAD (n = 35) as well as in 167 control subjects. Significant differences were observed for hs-CRP, TC, HDLc, LDLc, TG, ApoA-I, and ApoB levels, as well as for the ApoB/ApoA-I ratio, between the control and the IS or PAD groups. However, after adjustment for sex, age, smoking, hypertension, hs-CRP, and dyslipidemia (LDLc, TC, HDLc, TG, ApoA, ApoB, and ApoB/ApoA-I ratio), hs-CRP, ApoB, and the ApoB/ApoA-I ratio were independently associated with increased risks of IS or PAD. Increased ApoB/ApoA-I ratio and hs-CRP levels are independently associated with occurrence of IS and PAD in young patients and are significant markers of alterations on lipid and apolipoproteic profiles and inflammatory responses, respectively, in these patients.
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PMID:ApoB/ApoA-I ratio in young patients with ischemic cerebral stroke or peripheral arterial disease. 1877 40

Apolipoprotein E (apoE) is the primary apolipoprotein synthesized in the brain in response to injury with known neuroprotective effects exerted through antioxidant, antiinflammatory, antiexcitotoxic, and neurotrophic mechanisms. We have previously demonstrated that COG1410, an apoE mimetic peptide, exerts neuroprotective and antiinflammatory effects in a murine model of traumatic brain injury (TBI). As in TBI, ischemia-reperfusion injury is a component of acute stroke, which displays a pharmacogenetic association with the APOE4 gene. Using an intraluminal middle cerebral occlusion (MCAO) model in rats, we found that a single intravenous injection of COG1410 at 120 min post-MCAO significantly improved vestibulomotor function, decreased poststroke locomotor asymmetry, and decreased infarct volume of the ipsilateral hemisphere. These results support further exploration of a novel apoE-mimetic peptide, COG1410, as a therapeutic treatment for stroke.
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PMID:COG1410, a novel apolipoprotein-E mimetic, improves functional and morphological recovery in a rat model of focal brain ischemia. 1880 96

Apolipoprotein E (apoE), the major apolipoprotein in the central nervous system, has been shown to influence neurologic disease progression and response to neurologic injury in a gene-specific manner. Presence of the APOE4 allele is associated with poorer response to traumatic brain injury and ischemic stroke, but the association between APOE genotype and outcome following aneurysmal subarachnoid hemorrhage (SAH) remains unclear. The purpose of this project was to investigate the association between APOE genotype and outcome after SAH. We also explored the association of APOE4 genotype and cerebral vasospasm (CV) presence in a subsample of our population with available angiographic data. A sample of 206 aneurysmal SAH participants had APOE genotyping performed, Glasgow outcome scores (GOS) and modified Rankin scores (MRS) collected at 3 and 6 months after aneurysm rupture. No significant association was found between the presence of the APOE4 genotype and functional outcomes controlling for age, race, size of hemorrhage (Fisher grade), and severity of injury (Hunt & Hess grade). However when controlling for CV and the covariates listed above, individuals with the APOE4 allele had worse functional outcomes at both time points. The presence of the APOE2 allele was not associated with functional outcomes even when considering presence of CV. There was no difference in mortality associated with APOE4 presence, APOE2 presence, or presence of CV. These findings suggest APOE4 allele is associated with poor outcome after aneurysmal SAH.
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PMID:APOE genotype and functional outcome following aneurysmal subarachnoid hemorrhage. 1901 69

A 34-year-old African American woman with sickle cell disease and history of relatively severe hemolysis, chronic leg ulcers, and mild pulmonary hypertension presented with a new ischemic stroke. Recent research has suggested a syndrome of hemolysis-associated vasculopathy in patients with sickle cell disease, which features severe hemolytic anemia and leads to scavenging of nitric oxide and its biochemical precursor l-arginine. This diminished bioavailability of nitric oxide promotes a hemolysis-vascular dysfunction syndrome, which includes pulmonary hypertension, cutaneous leg ulceration, priapism, and ischemic stroke. Additional correlates of this vasculopathy include activation of endothelial cell adhesion molecules, platelets, and the vascular protectant hemeoxygenase-1. Some known risk factors for atherosclerosis are also associated with sickle cell vasculopathy, including low levels of apolipoprotein AI and high levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. Identification of dysregulated vascular biology pathways in sickle vasculopathy has provided a focus for new clinical trials for therapeutic intervention, including inhaled nitric oxide, sodium nitrite, L-arginine, phosphodiesterase-5 inhibitors, niacin, inhaled carbon monoxide, and endothelin receptor antagonists. This article reviews the pathophysiology of sickle vasculopathy and the results of preliminary clinical trials of novel small-molecule therapeutics directed at abnormal vascular biology in patients with sickle cell disease.
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PMID:Evolution of novel small-molecule therapeutics targeting sickle cell vasculopathy. 1906 84

Prothrombotic and proatherogenic risk factors, including elevated lipoprotein (a), predispose an individual to initial and recurrent ischemic stroke. An increased plasma level of lipoprotein (a), over 25-30 mg/dL, is called hyperlipoprotein (a)-emia, and is largely determined by genetic polymorphisms in apolipoprotein (a). Apolipoprotein (a) is a major protein component of lipoprotein (a), and is connected with apolipoprotein B-100 of low density lipoprotein. The size of apolipoprotein (a) and concentration of lipoprotein (a) vary widely among individuals as well as between ethnic groups. The size of apolipoprotein (a) and plasma concentrations of lipoprotein (a) are inversely related. Accordingly, the number of tandemly repeated structures, named kringle-4 domains, determines the size of apolipoprotein (a), and consequently the plasma lipoprotein (a) level. In addition, the efficiency of apolipoprotein (a) gene expression is a determinant of lipoprotein (a) concentrations, since lipoprotein (a) levels vary more than 200-fold even among the individuals having the same apolipoprotein (a) size. First, we identified haplotypes in the 5'-promoter region of the apolipoprotein (a) gene as a regulating factor of plasma lipoprotein (a) levels. Second, a pentanucleotide repeat polymorphism upstream of the promoter region was also reported to affect plasma lipoprotein (a) levels. Third, two functional single nucleotide polymorphisms were identified in a distal enhancer region situated approximately 20 kb from the apolipoprotein (a) gene. Finally, several polymorphisms were identified in the kringle-4 domains, and found to influence plasma lipoprotein (a) levels as well as the lysine/fibrin-binding function. Since lower molecular weight forms of apolipoprotein (a) are closely associated with the incidence of ischemic stroke, both high plasma concentrations of lipoprotein (a) and small sizes (i. e., number of kringle-4 repeats in the gene) of apolipoprotein (a) are risk factors for the development of atherothrombosis.
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PMID:[Hyperlipoprotein (a)-emia determined by genetic polymorphisms in apolipoprotein (a) gene]. 1906 64


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