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

The role of endothelin-1 (ET-1) in cerebral ischemic injury remains the subject of much debate. Vasoconstriction in large conduit vessels may not be associated with reductions in flow at the tissue level. We present two studies examining the effects on local cerebral blood flow of topical application of ET-1 to the surgically exposed middle cerebral artery (MCA) in adult male Sprague-Dawley rats. In the first series using 14C-iodoantipyrine autoradiography, 10 min following application of ET-1 (1 nmol) to the MCA, up to 80% reduction in blood flow in the territory of distribution of the MCA is seen (e.g., dorsolateral caudate nucleus--flow reduced from 131 +/- 3 ml/100 g/min to 29 +/- 25 ml/100 g/min). These levels of flow are comparable with those seen with permanent bipolar diathermy occlusion and division of the proximal MCA--a standard rat model of focal cerebral ischemia. In a second series using hydrogen clearance technique for measurement of local cerebral blood flow in the caudate nucleus, we have shown that flow ipsilateral to application of ET-1 (0.25 nmol) is significantly reduced compared with saline controls for 80 min. Such reduction of flow, at the tissue level, sustained over this duration is consistent with the induction of ischemic cell damage by ET-1.
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PMID:Reduction in local cerebral blood flow induced by endothelin-1 applied topically to the middle cerebral artery in the rat. 172 79

The central hemodynamic effects of the peptide endothelin-1 (ET-1) have been investigated in the conscious, normotensive rat. Intracisternal administration of ET-1 (0.01-0.03 nmol) gave rise to an increase in mean arterial pressure with minimal effects on heart rate and was accompanied in some cases by barrel rolling activity. Intracisternal administration of 0.03 nmol ET-1 gave rise to a significant elevation in plasma noradrenaline and adrenaline levels. This elevation in plasma catecholamines was present only in those animals that also exhibited marked behavioral changes. Autoradiographic measurement of cerebral blood flow carried out during the maximum response to 0.03 nmol of intracisternal ET-1 revealed a widespread and profound ischemia throughout the caudal brainstem. Cerebral ischemia is known to activate compensatory circulatory reflexes in the medulla oblongata that result in increased sympathetic and vagal outflow. This is the most likely cause of intracisternal ET-1-induced hypertension. ET-1 is unique in its ability to override the brain's autoregulatory mechanisms and induce ischemia of pathological magnitude.
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PMID:Endothelin-1-induced hypertension: a consequence of medullary ischemia? 172 22

The role of endothelin-1 (ET-1) in the failure of cerebral circulation after cardiac arrest is unknown. We evaluated the effect of complete global cerebral ischemia that was induced on the plasma ET-1 concentration in 5 dogs, by occluding the ascending aorta and caval veins for 15 min. A fiberoptic catheter was inserted into the sagittal sinus for the continuous monitoring of venous oxygen saturation. Blood samples were collected before and at 0.5, 1, 2, 4, and 6 h after the ischemic insult. The ET-1 concentration in the sagittal sinus and abdominal aorta was assayed. Complete global cerebral ischemia resulted in a significant 3-fold increase in the sagittal sinus concentration of ET-1 (P < 0.01) that was associated with a significant decrease in the sagittal sinus venous oxygen saturation (P < 0.01); the arterial ET-1 concentration remained unchanged. The difference between arterial and venous ET-1 concentrations during the hypoperfusion phase subsequent to the ischemic insult may result from an increased secretion of ET-1 by the cerebrovasculature and a decrease in the clearance of ET-1 in the cerebral circulation. The result suggests that ET-1 may contribute to the failure of cerebral circulation after cardiac arrest.
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PMID:Role of endothelin-1 in the failure of cerebral circulation after complete global cerebral ischemia. 748 Nov 5

The reversal of endothelin-1 induced cerebral vasospasm with Iloprost was studied in the rabbit. Vasospasm in the basilar artery was evaluated by angiography; cerebral ischaemia by 'red-neurone-count' on light microscopy and morphological changes by electron microscopy. A potent antagonistic effect of Iloprost against ET-1 was observed in each of the parameters measured.
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PMID:Alteration by Iloprost of the vasospastic effects of endothelin-1 in rabbit cerebral vessels. 752 81

1. We have recently developed a new model of transient focal ischaemia in the rat utilising topical application of endothelin-1 to the left middle cerebral artery (MCA). In order to validate this approach the present study assessed the neuroprotective efficacy of the NMDA receptor antagonist dizocilpine (MK-801) in the endothelin-1 model. The anti-ischaemic efficacy of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was subsequently evaluated, and contrasted with its efficacy against permanent focal ischaemia, to determine the utility of the endothelin-1 model for identification of novel pharmacoprotective agents. 2. MK-801 (0.12 mg kg-1 bolus, 108 micrograms kg-1 h-1 infusion i.v., either 1 or 2.5 h pre-transient MCA occlusion (MCAO)) induced hypotension that persisted for approximately 1.5 h so that mean arterial blood pressure (MABP) at the time of MCAO was significantly lower in the 1 h group compared with control (MABP: 86 +/- 11, 68 +/- 6 and 84 +/- 4 mmHg (mean +/- s.d.) for saline, 1 h MK-801 and 2.5 h MK-801 groups respectively). The 2.5 h pretreatment schedule resulted in significant reduction (71%) in the volume of hemispheric damage (assessed 4 h post onset of ischaemia) while the 1 h pretreatment schedule did not (volumes of hemispheric damage: 59 +/- 38, 51 +/- 51 and 17 +/- 28 mm3 for saline, 1 h and 2.5 h MK-801 groups). 3. Thus the considerable neuroprotective effect of MK-801 in the endothelin-1 model of transient focal cerebral ischaemia was highly sensitive to drug-induced hypotension. This result is in contrast to previous studies of permanent MCAO where MK-801-induced hypotension did not compromise its neuroprotective action.4. L-NAME (3 mg kg-1, i.v. 30 min pre-MCAO) moderately, but significantly, reduced (16%) the volume of ischaemic damage 4 h post-permanent MCA occlusion, whereas the 29% reduction in volume of damage achieved in the model of transient focal ischaemia did not attain significance due to the greater variability associated with this model. L-NAME did not significantly alter MABP in either model.5. The modest neuroprotection achieved with NO synthase inhibition suggests NO is of relatively minor importance as a mediator of neurotoxicity following permanent focal cerebral ischaemia. In addition the comparable efficacy of L-NAME against transient focal ischaemia suggests the presence of reperfusion does not enhance the contribution of NO to neuronal injury in the acute (4 h) phase following a focal ischaemic insult.
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PMID:Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-D-aspartate receptor antagonist in models of transient and permanent focal cerebral ischaemia. 752 11

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

The regulatory role of endothelins in cerebral microvessels was investigated in a recently developed model system which allows the study of small cerebral vessels in their normal microenvironment. Using brain slices of the rat neocortex, it was shown that the isopeptide endothelin-3 (ET-3) had no effect on cerebral microvessels, while the isopeptide endothelin-1 (ET-1) produced a potent, dose-dependent vasoconstriction. When a recently developed antagonist of ETA receptors (cyclo-[D-Asp-L-Pro-D-Val-L-Leu-D-Trp]; ETant) was administered prior to treatment with ET-1, the vasoconstrictor response to ET-1 was inhibited in a dose-dependent manner. When ETant was administered after the establishment of a constriction by ET-1, the constrictor response to ET-1 was partially reversed, and this effect was weaker than that seen in the pre-treatment paradigm. These findings indicate that constrictor responses to ET-1 in cerebral microvessels are mediated by ETA receptors. Inasmuch as endothelins have been implicated in pathological forms of vasoconstriction in the CNS, the present findings also suggest that endothelin antagonists may be useful in the treatment of cerebral ischemia.
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PMID:Cerebral microvascular responses to endothelins: the role of ETA receptors. 783 40

In acute cerebral ischemia there are severe damages of endothelium recognized as the stimuli for secretion of endothelin-1, that is a endothelium-derived peptide and seems to be the most potent vasoconstrictor known. The goal of this study is to measure plasma endothelin-1 level in patients with cerebral infarction and determine the relationship between endothelin-1 and ischemic stroke. Plasma level of endothelin-1 was measured in 21 consecutive patients. The measurement was performed 3 times at different stages of stroke. There was a marked increase in plasma endothelin-1 level in the patients and the elevation lasted the entire acute and subacute stage of stroke. There was a correlation between the peptide concentration and infarct volume (r = 0.665, P < 0.01). The result suggests that endothelin-1 plays an important role in the regulation of brain circulation. Apparent and lasting increase in plasma level of endothelin-1 is associated with cerebral ischemia and infarction. The peptide seems to be involved in the pathophysiology of acute cerebral ischemia and have a deleterious effect in the evolution of cerebral infarction.
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PMID:[Increased plasma endothelin-1 concentration in acute cerebral infarction and its clinical significance]. 786 29

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

Endothelin-mediated vasoconstriction may theoretically aggravate ischemic neuronal damage. Although investigators have demonstrated that endothelins are produced by cerebral microvessel endothelial cells, astrocytes and neurons in vitro, whether endothelins are produced during cerebral ischemia is still unclear. The purpose of this study, therefore, was to measure endothelin-1 in brain tissue and plasma following middle cerebral artery occlusion and to examine the relationship between brain tissue and plasma endothelin-1 levels. The middle cerebral artery of rabbits was occluded for 2, 4 or 24 h. The amount of endothelin-1 in both brain tissue and plasma was determined by RIA. The results demonstrate that the concentrations of endothelin-1 in the ischemic brain tissue and plasma are both significantly increased after focal cerebral ischemia (P < 0.01). The data confirm that an acute and marked increase of endothelin-1 in brain tissue and plasma is associated with focal ischemic events. The possibility that endothelin-1 has a role in neuronal cell damage following focal ischemia warrants further attention.
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PMID:Increased endothelin-1 in the rabbit model of middle cerebral artery occlusion. 797 Jan 53


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