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

There are increasing evidences that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders including hypertension. Docosahexaenoic acid (DHA) may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study was to clarify the in vitro effect of DHA on vascular smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca+2 dynamics which involves in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on the cell growth, and cell hypertrophy induced by angiotensin II as measured by flow cytometer. DHA did not have a significant effect on interleukin-1 beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in the intracellular Ca2+ concentration induced by 5-hydroxytryptamine, angiotensin II, depolarizing concentration of KCl, but not by thapsigargin. This suppression seems to be due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results suggest that DHA specifically suppresses receptor-mediated Ca2+ influx in smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.
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PMID:[Specific modulation of vascular smooth muscle cell functions by docosahexaenoic acid]. 950 27

There is increasing evidence that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders, including hypertension. Docosahexaenoic acid (DHA), may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study is to clarify the in vitro effect of DHA on cultured smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca2+ metabolism, which are involved in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on cell growth or on cell hypertrophy induced by angiotensin II as measured by flow cytometry. DHA had no stimulatory effect on interleukin-1beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP, but rather slightly inhibited it. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in intracellular Ca2+ concentration induced by angiotensin II, but not by thapsigargin. This was due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results indicate that DHA specifically suppresses Ca2+ mobilization into smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.
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PMID:Effect of docosahexaenoic acid on smooth muscle cell functions. 958 58

Docosahexaenoic acid (DHA) is an n-3 unsaturated fatty acid derived from fish oils. The precise mechanisms of DHA actions are still obscure. Especially, the antihypertensive effect of DHA has not yet been elucidated. Stroke-prone spontaneously hypertensive rats (SHRSP) provide the best available model for essential hypertension and stroke. The present study was undertaken to elucidate the effects of long term administration of DHA on blood pressure and stroke-related behavior in SHRSP. The blood pressure of DHA-treated SHRSP was lowered significantly as compared with that of non-treated SHRSP. DHA produced an ameliorative effect on the decreased passive avoidance response in SHRSP. DHA also improved the behavioral changes in spontaneous motor activity of SHRSP. DHA-treated SHRSP produced a significant decrease in the levels of total cholesterol, low density lipoprotein, triglycerides, lipid peroxide, serum creatinine and blood urea nitrogen as compared with those in non-treated SHRSP. These findings indicate that the DHA-induced antihypertensive action may be associated with the amelioration of both serum lipid alteration and renal dysfunction in non-treated SHRSP. Moreover, DHA-treated SHRSP maintain the normal levels of acetylcholine and choline concentrations in the hippocampus and cerebral cortex. These findings demonstrated that DHA produced an ameliorative effect on cholinergic nerve dysfunction in SHRSP. The improved cholinergic nerve function induced by DHA might have an inhibitory effect on stroke-related behavior in SHRSP. The present study suggests that long term administration of DHA may suppress the development of hypertension and stroke-related behavioral changes in SHRSP.
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PMID:[Antihypertensive effect of docosahexaenoic acid in stroke-prone spontaneously hypertensive rats]. 1092 Jul 15

Ischemic stroke triggers lipid peroxidation and neuronal injury. Docosahexaenoic acid released from membrane phospholipids during brain ischemia is a major source of lipid peroxides. Leukocyte infiltration and pro-inflammatory gene expression also contribute to stroke damage. In this study using lipidomic analysis, we have identified stereospecific messengers from docosahexaenoate-oxygenation pathways in a mouse stroke model. Aspirin, widely used to prevent cerebrovascular disease, activates an additional pathway, which includes the 17R-resolvins. The newly discovered brain messenger 10,17S-docosatriene potently inhibited leukocyte infiltration, NFkappaB, and cyclooxygenase-2 induction in experimental stroke and elicited neuroprotection. In addition, in neural cells in culture, this lipid messenger also inhibited both interleukin 1-beta-induced NFkappaB activation and cyclooxygenase-2 expression. Thus, the specific novel bioactive docosanoids generated in vivo counteract leukocyte-mediated injury as well as pro-inflammatory gene induction. These results challenge the view that docosahexaenoate only participates in brain damage and demonstrate that this fatty acid is also the endogenous precursor to a neuroprotective signaling response to ischemia-reperfusion.
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PMID:Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. 1292

The central nervous system has the second highest concentration of lipids after adipose tissue. Long chain fatty acids, particularly arachidonic acid and docosahexaenoic acid, are integral components of neural membrane phospholipids. Alterations in neural membrane phospholipid components cannot only influence crucial intracellular and intercellular signaling but also alter many membrane physical properties such as fluidity, phase transition temperature, bilayer thickness, and lateral domains. A deficiency of docosahexaenoic acid markedly affects neurotransmission, membrane-bound enzyme and ion channel activities, gene expression, intensity of inflammation, and immunity and synaptic plasticity. Docosahexaenoic acid deficiency is associated with normal aging, Alzheimer disease, hyperactivity, schizophrenia, and peroxisomal disorders. Although the molecular mechanism of docosahexaenoic acid involvement in the disorders remains unknown, the supplementation of docosahexaenoic acid in the diet restores gene expression and modulates neurotransmission. Also, improvements are seen in signal transduction processes associated with behavioral deficits, learning activity, peroxisomal disorders, and psychotic changes in schizophrenia, depression, hyperactivity, stroke, and Alzheimer disease.
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PMID:Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. 1504 Oct 28

Synaptic activity and ischemia/injury promote lipid messenger formation through phospholipase-mediated cleavage of specific phospholipids from membrane reservoirs. Lipid messengers modulate signaling cascades, contributing to development, differentiation, function (e.g., memory), protection, regeneration, and repair of neurons and overall regulation of neuronal, glial, and endothelial cell functional integrity. Oxidative stress disrupts lipid signaling and promotes lipid peroxidation and neurodegeneration. Lipid signaling at the neurovascular unit (neurons, astrocytes, oligodendrocytes, microglia, and cells of the microvasculature) is altered in early cerebrovascular and neurodegenerative disease. We discuss how lipid signaling regulates critical events in neuronal survival. Aberrant synaptic plasticity (e.g., epileptogenesis) is highlighted to show how gene expression may drive synaptic circuitry formation in the "wrong" direction. Docosahexaenoic acid has been implicated in memory, photoreceptor cell biogenesis and function, and neuroprotection. Free docosahexaenoic acid released in the brain during experimental stroke leads to the synthesis of stereospecific messengers through oxygenation pathways. One messenger, 10,17S-docosatriene (neuroprotectin D1; NPD1), counteracts leukocyte infiltration and proinflammatory gene expression in brain ischemia-reperfusion. In retina, photoreceptor survival depends on retinal pigment epithelial (RPE) cell integrity. NPD1 is synthesized in RPE cells undergoing oxidative stress, potently counteracts oxidative stress-triggered apoptotic DNA damage in RPE, upregulates antiapoptotic proteins Bcl-2 and Bcl-x(L), and decreases proapoptotic Bax and Bad expression. These findings expand our understanding of how the nervous system counteracts redox disturbances, mitochondrial dysfunction, and proinflammatory conditions. The specificity and potency of NPD1 indicate a potential target for therapeutic intervention for stroke, age-related macular degeneration, spinal cord injury, and other neuroinflammatory or neurodegenerative diseases.
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PMID:Brain response to injury and neurodegeneration: endogenous neuroprotective signaling. 1617 16

1. Population studies and clinical trials provide compelling evidence that omega-3 (omega3) fatty acids have cardioprotective effects. The strongest evidence is from DART and GISSI-P, two secondary prevention trials in patients with previous myocardial infarctions. Data from these trials support a reduction in ventricular fibrillation as a primary mechanism for the decreased incidence of myocardial infarction. 2. Evidence suggests that w3 fatty acids may also provide protection against stroke, particularly ischaemic stroke. 3. The cardioprotective effects of omega3 fatty acids relate to improvements in blood pressure, cardiac function, arterial compliance and vascular function, as well as improved lipid metabolism, antiplatelet and anti-inflammatory effects. 4. Clinical trials in humans have shown that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have different haemodynamic properties. Docosahexaenoic acid may be more favourable in lowering blood pressure and heart rate, as well as improving vascular function. However, the effects of EPA and DHA may also differ depending on the target population.
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PMID:Omega-3 fatty acids and hypertension in humans. 1692 18

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have beneficial effects on cardiovascular function. We tested the hypotheses that dietary supplementation with DHA (2 g/day) + EPA (3 g/day) enhances increases in stroke volume (SV) and cardiac output (CO) and decreases in systemic vascular resistance (SVR) during dynamic exercise. Healthy subjects received DHA + EPA (eight men, four women) or safflower oil (six men, three women) for 6 weeks. Both groups performed 20 min of bicycle exercise (10 min each at a low and moderate work intensity) before and after DHA + EPA or safflower oil treatment. Mean arterial pressure (MAP), heart rate (HR), SV, CO, and SVR were assessed before exercise and during both workloads. HR was unaffected by DHA + EPA and MAP was reduced, but only at rest (88 +/- 5 vs. 83 +/- 4 mm Hg). DHA + EPA augmented increases in SV (14.1 +/- 6.3 vs. 32.3 +/- 8.7 ml) and CO (8.5 +/- 1.0 vs. 10.3 +/- 1.2 L/min) and tended to attenuate decreases in SVR (-7.0 +/- 0.6 vs. -10.1 +/- 1.6 mm Hg L(-1) min(-1)) during the moderate workload. Safflower oil treatment had no effects on MAP, HR, SV, CO or SVR at rest or during exercise. DHA + EPA-induced increases in SV and CO imply that dietary supplementation with these fatty acids can increase oxygen delivery during exercise, which may have beneficial clinical implications for individuals with cardiovascular disease and reduced exercise tolerance.
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PMID:Omega-3 fatty acid supplementation enhances stroke volume and cardiac output during dynamic exercise. 1856 35

Docosahexaenoic acid (DHA), the main omega-3 fatty acid, is concentrated and avidly retained in membrane phospholipids of the nervous system. DHA is involved in brain and retina function, aging, and neurological and psychiatric/behavioral illnesses. Neuroprotectin D1 (NPD1), the first-identified stereoselective bioactive product of DHA, exerts neuroprotection in models of experimental stroke by down-regulating brain ischemia reperfusion (BIR)-induced leukocyte infiltration, proinflammatory signaling, and infarct size. Moreover, NPD1 inhibits cytokine-mediated cyclooxygenase-2 (COX-2) expression. Photoreceptor membranes display the highest content of DHA of any cell. Retinal pigment epithelial cells participate in the phagocytosis of the tips of photoreceptor cells (photoreceptor outer segment renewal). There is a DHA retrieval-intercellular mechanism between both types of cells that conserves this fatty acid during this process. NPD1 promotes homeostatic regulation of the integrity of these two cells, particularly during oxidative stress, and this protective signaling may be relevant in retinal degenerative diseases. Moreover, neurotrophins are NPD1-synthesis agonists, and NPD1 content is decreased in the CA1 region of the hippocampus of Alzheimer's patients. Overall, NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Abeta42 production and its neurotoxicity. Thus, NPD1 elicits potent cell-protective, anti-inflammatory, prosurvival repair signaling.
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PMID:Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease. 1901 37

Mediator lipidomics is a field of study concerned with the characterization, structural elucidation and bioactivity of lipid derivatives actively generated by enzymatic activity. It is well known that omega-3 fatty acids are beneficial for brain function. Docosahexaenoic acid [DHA; 4 22:6(n-3)] is the most abundant essential omega-3 fatty acid present in the brain and it has multiple mechanisms of exerting protective effects after cellular injury. Certain lipid species produced from DHA early during the reperfusion stage of brain ischemia-reperfusion injury are generated in order to help the cell cope as the injury progresses. We explore these newly discovered lipid mediators in order to understand their role in the cell. We have identified one of these potentially protective lipid mediators as a novel stereospecific DHA-derived fatty acid, called neuroprotectin D1 (NPD1; 10R,17S-dihydroxy-docosa-4Z,7Z,11E,15E,19Z hexaenoic acid). DHA also has important roles in pro-survival signaling cascades after ischemia-reperfusion in injury. It has been shown to accelerate AKT translocation and activation and has binding affinity with an important PPAR-gamma family of ligand-activated nuclear receptors that have been implicated in various aspects of lipid metabolism and have been shown to have anti-inflammatory actions. Here we present an overview of these mechanisms and discuss the potential of using DHA signaling in the development of treatments for the large population of patients suffering from the devastating consequences of stroke.
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PMID:Docosahexaenoic acid neurolipidomics. 1980 38


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