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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Information about the presence of the endothelin system in the cerebrovascular bed and its physiological or pathophysiological role(s) in the control of the cerebral circulation has dramatically increased in recent years. Endothelin-1 can be produced in the cerebrovascular bed from circulating big endothelin or by endogenous endothelin mRNA expression. Endothelins bind to specific ETA and ETB receptors in cerebral vessels. Activation of these receptors triggers intracellular signal transduction mechanisms mediating tone maintenance as well as long-term vascular changes. Endothelins are potent constrictors of cerebral arteries isolated from different species, including humans. In vivo the reductions in vessel diameter or blood flow due to the direct vasoconstrictive effects of endothelin-1 are modulated or even changed in some cases to opposite vasodilatative effects because of the release of dilatative substances. The ability of locally applied endothelin-1 to reduce blood flow to pathologically low levels has been used to develop animal models of focal cerebral ischemia. Endothelin-1 is thought to play a role in the pathophysiology of nonhemorrhagic cerebral infarct and in cerebral vasospasm after subarachnoid hemorrhage.
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PMID:Endothelins and the cerebral circulation. 766 92

Endothelin-1 (ET-1) is a 21 aminoacid peptide with potent vasoconstrictor properties. It is synthesised and released by endothelial cells in both the peripheral and cerebral vasculature and is also localised within neurones in discrete brain areas where it may contribute to the central regulation of blood pressure. We have shown that intracisternal ET-1 in conscious rats induces a marked pressor response that is associated with an intense widespread reduction in cerebral blood flow. Subsequent studies with local application of ET-1 to the middle cerebral artery (MCA) revealed a dose dependent reversible vasoconstriction of the artery that resulted in profound reductions in local cerebral blood flow and the development of cerebral infarction. Thus abluminal application of ET-1 to the MCA offers a simple model of reversible focal cerebral ischaemia in the rat that complements the existing models of permanent MCA occlusion. The ET-1 model will help to provide new insights into the mechanisms of cerebral ischaemia and reperfusion injury, and to evaluate the usefulness of novel strategies of neuroprotection.
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PMID:Endothelin, cerebral ischaemia and infarction. 773 85

Vasoactive factors produced and released by the endothelium exert a powerful influence on vascular tone in the cerebral circulation. Impaired endothelium-dependent responses, such as decreased production of endothelium-derived relaxing factors, and/or release of endothelium-derived contractile factors may give rise to different pathophysiological conditions. Among the endothelium-derived contractile factors the endothelins have recently received particular attention. Endothelin-1 is the major isoform in the endothelin family, which also includes endothelin-2 and endothelin-3. Endothelin-1 is synthesized within the endothelium of cerebral vessels, whereas both endothelin-1 and endothelin-3 in addition have been identified in neurons and glia. Recent electrophysiological work has suggested a neuromodulatory role for these peptides, but at present the general interest is mainly focused on their vasoactive role. Physiological stimuli such as hypoxia, anoxia, and hemodynamic shear stress will stimulate the endothelial endothelin production. In the brain, at least two types of specific subreceptors have been cloned; ETA receptors, exclusively associated with blood vessels and ETB receptors also found on glial, epithelial, and ependymal cells. The endothelins seem so far to be the most potent vasoconstrictors yet identified. The circulating plasma levels of immunoreactive endothelin are low. Since more than 80% of the total amount released from endothelial cells seems to be secreted towards the underlying smooth muscle, endothelins have been ascribed a local vasoregulatory role. Endothelins are believed to be involved in several of our most common cerebrovascular diseases and the present review comments on their possible pathophysiological role in subarachnoid haemorrhage, cerebral ischemia, and migraine.
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PMID:Endothelins: a role in cerebrovascular disease? 795 53

In acute cerebral ischemia there are severe damages of endothelium which have been recognized as the stimuli to secrete endothelin-1, an endothelium-derived peptide and the most potent vasoconstrictor ever known. This study was to measure plasma endothelin-1 level in patients with cerebral infarction and explore the relationship between endothelin-1 and ischemic stroke. The possible involvement of endothelin-1 in local regulation of cerebral arterioles was also investigated. Plasma levels of endothelin-1 were measured by radioimmunoassay in 21 patients. Using a micro-video system, the endothelin-1 actions were also observed on rat pial arterioles in vivo, and with incomplete cerebral ischemia model (rat), effect of ischemia affects the endothelin-1 action. There was a marked increase in plasma endothelin-1 level in the patients and the elevation persisted during the acute and subacute period of stroke. There was a positive correlation between the peptide concentration and infarct size (r = 0.655, P < 0.01). In rats, endothelin-1 (dose range: 10(-10) mole/L-10(-7) mole/L) induced a dose-dependent arteriole contraction after subdural administration. Arteriole calibers were decreased by 27.7% +/- 3.8% (10(-9) mole/L), 46.8% +/- 4.9% (10(-8) mole/L) and 78.5% +/- 4.7% (10(-7) mole/L), respectively. Cerebral ischemia significantly enhanced the action of endothelin-1 (96.4% +/- 7.2% vs 58.2% +/- 6.8%). Endothelin-1 plays an important role in regulating local circulation of ischemic brain. The notable and lasting increase in plasma level of endothelin-1 are associated with cerebral ischemia and infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased plasma endothelin-1 concentration in patients with acute cerebral infarction and actions of endothelin-1 on pial arterioles of rat. 814 9

In a model of focal cerebral ischemia in mice, intracisternal injection of 5 and 10 pmol/mouse endothelin-1 significantly increased the infarcted surface area by 15.5% and by 23.5%, respectively. Endothelin-1 (0.01, 1, and 100 nmol/l) added to the primary neuronal cultures of chick embryo cerebral hemispheres for 1 h and 24 h did not influence the viability of the neurons or the protein content of the cultures. When applied simultaneously with 1 mmol/l sodium cyanide for 30 min, endothelin-1 (0.01, 1, and 100 nM) did not modify the hypoxia-induced changes. The results show that exogenously applied endothelin-1 could exacerbate cerebral ischemia, probably due to its vasoconstrictive properties and not to a direct neurotoxic effect.
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PMID:Endothelin-1 exacerbates focal cerebral ischemia without exerting neurotoxic action in vitro. 822 67

Endothelin-1 (ET-1) plays an important role in the physiologic or pathophysiologic regulation of cerebral circulation. To evaluate the effect of mild hypothermia on the cerebral concentration of ET-1 and on the cerebral metabolism of oxygen after complete global cerebral ischemia, we occluded the ascending aorta and caval veins of 9 dogs for 15 min. A fiberoptic catheter was inserted into the sagittal sinus to monitor venous oxygen saturation (S(SO)2) continuously. Blood samples were collected 30 min before and 30 min, 1 h, 2 h, 4 h and 6 h after the ischemic insult. Concentrations of ET-1 were assayed in the blood of the sagittal sinus and abdominal aorta. Before, during and after the aortic occlusion, we compared findings in a normothermic control Group 1 (pulmonary artery temperature 38.5 degrees C) (n = 4) with those in the mildly hypothermic Group 2 (pulmonary artery temperature 34.0 degrees C) (n = 5) by surface cooling induced before and maintained during and after ischemia for 6 h. Following ischemia, the plasma concentration difference of ET-1 (sagittal sinus--arterial) was significantly decreased in Group 2 (P < 0.05). Differences in S(SO)2 between the two groups were not statistically significant. Mild hypothermia reduced the ET-1 release in the cerebral circulation but did not improve cerebral oxygen metabolism after complete cerebral ischemia. Findings indicated that the decrease in ET-1 induced by mild hypothermia contributes to the improvement of the cerebral microcirculation after ischemia.
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PMID:Effect of mild hypothermia on ischemia-induced release of endothelin-1 in dog brain. 870 Nov 10

In order to study the consequences of reperfusion for ischaemic brain injury, quantitative ligand binding autoradiography was carried out in a model of reversible focal cerebral ischaemia. Endothelin-1 applied to the abluminal surface of the middle cerebral artery in anaesthetized Sprague-Dawley rats induced severe focal ischaemia and subsequent reperfusion (assessed by blood flow tracers [99mTc]HMPAO and [14C]iodoantipyrine respectively) by 2 h after insult. Ligand binding autoradiography on consecutive sections demonstrated these blood flow changes to be associated with a significant reduction in forskolin binding throughout the middle cerebral artery territory (e.g. 25% in parietal cortex, 11% in dorsolateral caudate nucleus). The most marked losses in forskolin binding were in areas where ischaemia was severe and reperfusion was poor. However, the same changes in cerebral blood flow had no significant effect on D1 dopamine receptor binding (e.g. < 2% reduction in the caudate nucleus). These data demonstrate that ligand binding characteristics are significantly affected as early as 2 h after insult, with evidence of differential sensitivity for forskolin and D1 dopamine binding. With regard to the consequences of reperfusion, comparison with our previous study of 2 h maintained ischaemia demonstrates reperfusion-related salvage of dopamine and forskolin binding in the caudate nucleus but possible exacerbation of forskolin binding loss in the cortex.
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PMID:Consequences of transient focal cerebral ischaemia for second messenger and neurotransmitter binding in the rat: quantitative autoradiographic analysis of forskolin, dopamine D1 receptor binding and cerebral blood flow changes. 896 39

Endothelin-1 (ET-1) plays an important role in the physiologic or pathophysiologic regulation of cerebral circulation. To evaluate the effects of the newly synthesized ETA receptor-selective antagonist, BQ-485 (N-perhydroazepin-l-ylcarbonyl-Leu-D-Trp-D-Trp-OH), on the cerebral metabolism of oxygen during the delayed cerebral hypoperfusion that follows global cerebral ischemia, we occluded the ascending aorta and caval veins of 10 beagle dogs for 12.5 min. The animals were randomized into two groups. BQ-485 was given directly into the carotid artery at 0.03 mg/kg per min for 30 min, starting 15 min after reperfusion in the treatment group (n = 5). Isotonic saline was infused in the control group (n = 5). A fiberoptic catheter was inserted into the superior sagittal sinus to monitor its oxygen saturation (SssO2) continuously. Arterial O2 content (CaO2), and sagittal sinus O2 content (CssO2) were monitored before and at 0.5, 1, 2, 4, 6 and 8 h after the ischemic insult. BQ-485 significantly prevented the expected decrease in SssO2 and increase in the cerebral O2 utilization coefficient at 4, 6 and 8 h after the ischemic insult (P < 0.05). Thus, BQ-485 ameliorated the mismatch between O2 supply and demand in the delayed hypoperfusion phase. We conclude that ET may be involved in the pathogenesis of delayed cerebral hypoperfusion after cardiac arrest.
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PMID:Effect of an endothelin-1 antagonist, BQ-485, on cerebral oxygen metabolism after complete global cerebral ischemia in dogs. 905 26

Despite years of research, delayed cerebral vasospasm remains a serious complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis in a series of experiments. In a primate model of SAH, serial ET-1 levels were measured in samples from the perivascular space by using a microdialysis technique and in cerebrospinal fluid (CSF) and plasma during the development and resolution of delayed vasospasm. To determine whether elevated ET-1 production was a direct cause of vasospasm or acted secondary to ischemia, the authors also measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To elucidate the source of ET-1, they measured its production in cultures of endothelial cells and astrocytes exposed to oxyhemoglobin (10 microM), methemoglobin (10 microM), or hypoxia (11% oxygen). There was no correlation between the perivascular levels of ET-1 and the development of vasospasm or its resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by vasospasm (CSF ET-1 levels were 9.3 +/- 2.2 pg/ml and ET-1 plasma levels were 1.2 +/- 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 +/- 1.7 pg/ml in CSF and 2.7 +/- 1.5 pg/ml in plasma). Transient cerebral ischemia evoked an increase of ET-1 levels in CSF (1 +/- 0.4 pg/ml at the occlusion vs. 3.1 +/- 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal (0.7 +/- 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture showed inhibition of ET-1 production 6 hours after exposure to hemoglobins. Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 +/- 0.8 pg/ml vs. 0.1 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05) and at 48 hours (6.4 +/- 0.6 pg/ml vs. 0 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET-1 at 6 hours (1.5 +/- 0.6 vs. 6.4 +/- 1.1 pg/ml, control vs. hypoxic astrocytes; p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells, during hypoxia and is released from the brain after transient ischemia. There is no relationship between ET-1 and vasospasm in vivo or between ET-1 and oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1 levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the result of cerebral ischemia rather than reflecting the cause of cerebral vasospasm.
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PMID:Source and cause of endothelin-1 release into cerebrospinal fluid after subarachnoid hemorrhage. 925 95

Endothelin-1 (ET-1) gene expression of rat brain during ischemia and reperfusion as well as the effect of Radix Salviae Miltiorrhizae (RSM) were studied with in situ hybridization. It was found that ET-1 gene expression of cerebral cortex and caudate-putamen was markedly increased both in 24 hours of ischemia and 24 hours of reperfusion groups (P < 0.01, P < 0.05). In RSM-treated rats, although the ET-1 gene expressions of ischemia and reperfusion sides were also increased as compared with contralateral cortex and caudate-putamen, they were significantly lower in RSM-treated rats than those of controls (P < 0.05, P < 0.01 respectively). The present study indicated that RSM can partly inhibit ET-1 gene expression of cerebral cortex and caudate-putamen during ischemia and reperfusion. This may be one of the protective mechanisms of RSM on cerebral ischemia and reperfusion.
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PMID:ET-1 gene expression of rat brain during ischemia and reperfusion and the protective effect of radix Salviae miltiorrhizae. 1043 50


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