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

Dopamine (DA), serotonin (5-HT), tryptophan (TRP), 5-hydroxyindole acetic acid (5-HIAA), and GABA were assayed spectrofluorometrically in various regions of 16 human post-mortem brains with acute and old cerebral infarction. In both recent and older strokes a total depletion of DA and 5-HT in the necrotic tissue was associated with mild reduction of these compounds in remote non-ischemic areas of the injured, and less of the contralateral cerebral hemispheres. 5-HIAA was significantly reduced in acute ischemic necrosis, while the perifocal edema zone showed considerable accumulation of both 5-HT and 5-HIAA. Marked elevation of the 5-HT precursor TRP and of GABA was present in both the necrotic center and perifocal edema of acute infarcts, which also showed a mild reduction of total proteins. The degradation zone surrounding old infarcts showed a mild decrease of both 5-HT and 5-HIAA with normal TRP levels, indicating normalization of the previously increased 5-HT metabolism and turnover after decrease of acute cerebral edema. These data which confirm previous studies in experimental cerebral ischemia and stroke indicate that disorders in the metabolism of brain monoamines and other putative neurotransmitters contribute to the development of postischemic brain damage and the complicating cerebral edema. They are also in keeping with the concept that unilateral focal ischemia produces bilateral effects on brain monoamines.
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PMID:Changes of some putative neurotransmitters in human cerebral infarction. 3 76

Dopamine (DA), serotonin (5-HT), and 5-hydroxyindole acetic aced (5-HIAA) were assayed spectrofluorometrically in various brain regions of 8 human patients who died after acute and old cerebral infarction. In both recent and older infarct a total depletion of DA and 5-HT was associated with slight reduction of DA and 5-HT levels in remote nonischemic areas and various nuclei of both the injured and contralateral hemispheres. 5-HIAA was significantly reduced in acute ischemic necrosis, while the perifocal edema zone showed considerable accumulation of both 5-HT and 5-HIAA. The degradation zone surrounding old infarcts showed a mild decrease of both 5-HT and 5-HIAA, indicating normalization of K-HT metabolism and turnover after decrease of cerebral edema. These preliminary data which confirm previous findings in experimental cerebral ischemia and infarct indicate that disorders of brain monoamine metabolism are contributing to the development of postischemic brain damage and the complicating cerebral edema.
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PMID:Brain monoamines in human cerebral infarcts. A preliminary study. 63 47

Alterations in brain tissue levels of monoamines and monoamine metabolites were studied in gerbils 60 min after cerebral ischemia induced by 10 min carotid ligation after pretreatment with the antiischemic drug DM-9384 (1, 3, 10, 30 mg/kg, PO). The DA levels decreased in striatum after the ischemia, while cortical and hippocampal DA levels increased. The DOPAC levels increased in cortex, but were essentially unaffected in other regions. The HVA levels increased in all forebrain regions studied. NA levels decreased in hippocampus and superior colliculus, while a general increase in MHPG levels was seen. Decreases in 5-HT levels were seen in all forebrain regions except cortex. The 10 mg/kg and 30 mg/kg doses of DM-9384 counteracted the decrease in striatal 5-HT and hypothalamic MHPG/NA ratio, respectively. Thus pretreatment with DM-9384 exerted minor protective effects on the alterations induced in monoamine systems by transient forebrain ischemia.
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PMID:Effects of DM-9384, a pyrrolidone derivative, on ischemia-induced changes in the central monoamine systems. 137 10

Excessive neuronal activity combined with an increased release of neurotransmitters is supposed to contribute to the delayed neuronal degeneration in animal models of transient cerebral ischemia. Since evidence is accumulating that serotonin (5-HT) exerts an excitatory effect on neurons via 5-HT2 receptors we tested the hypothesis that 5-HT2 receptor antagonists could protect neurons in the gerbil after transient bilateral carotid occlusion. In a first series of experiments, the 5-HT2 receptor antagonist ketanserin was injected intraperitoneally 15 min prior to 5 min of forebrain ischemia and given twice daily on the following 3 days. At a dose of 10 mg/kg i.p., the number of intact hippocampal CA1 neurons was significantly higher than in the saline-treated group and reached 74% of the sham-operated controls. In addition, the degree of neuronal damage correlated with an increased intracellular Ca2+ content in CA1 pyramidal neurons as revealed by arsenazo(III) staining with a procedure modified for paraffin sections. In a second series of experiments, ketanserin (10 mg/kg) was injected at various times after onset of ischemia. Up to a period of 90 min after ischemia, the number of intact CA1 pyramidal cells in ketanserin-treated animals was still significantly higher than in the saline-treated group. These results indicate that 5-HT2 receptor antagonists may protect neurons against ischemic damage even when the treatment is started after onset of ischemia. It remains to be investigated whether the neuroprotective effect of ketanserin is due to a neuronal action or to an inhibition of cerebrovascular vasospasm.
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PMID:Ketanserin reduces neuronal calcium accumulation and cell death in the hippocampus of the Mongolian gerbil after transient forebrain ischemia. 151 Dec 66

Changes in the levels of histamine, monoamines, and their metabolites in the cerebral cortex and striatum after occlusion of the middle cerebral artery in rats were examined. The water content of the ipsilateral brain regions gradually increased after occlusion. In the ischemic side, 1 h after occlusion, the cortical norepinephrine and striatal 5-hydroxy-tryptamine levels significantly decreased, and striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid levels markedly increased. In contrast, the levels of histamine and tele-methylhistamine in either brain region gradually increased and the changes became pronounced and statistically significant 6-12 h after induction of ischemia. The striatal histamine and tele-methylhistamine reached levels three- and twofold higher, respectively, than those of the contralateral side. In rats treated with alpha-fluoromethylhistidine 1 h before induction of ischemia, elevation of histamine and tele-methylhistamine was not observed. The elevated histamine level in the ipsilateral straitum at 9 h after occlusion was further significantly increased by the treatment with metoprine, an inhibitor of histamine-N-methyltransferase. These results suggest that the histaminergic activity in the brain is gradually enhanced by cerebral ischemia.
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PMID:Changes in the metabolism of histamine and monoamines after occlusion of the middle cerebral artery in rats. 205 Nov 72

Human platelets release two major classes of vasoactive mediators during the secretion reaction: arachidonic acid metabolites and biogenic amines. All of these compounds, in particular thromboxane A2, PGF2 alpha, and serotonin (5-HT), are potent constrictors of human cerebral arteries in vitro. This contractile action of platelet-derived vasoconstrictors, as well as their prothrombotic activity, is antagonized by the vascular endothelium. Atherosclerotic alterations of the vessel wall endothelium, typical for cerebral ischemia and stroke, are associated with platelet hyperreactivity and enhanced mediator release during stimulation. Inhibition of platelet (hyper)function by acetylsalicylic acid or ticlopidine has clear protective effects in high-risk patients, underlining the significance of these platelet-derived products for cerebral thromboembolism and vasoconstriction. Whether more selective inhibitors of thromboxane generations or action are equally effective remains to be determined.
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PMID:Platelets as a source of vasoactive mediators. 212 87

Cerebral ischemia induced by bilateral common carotid artery occlusion (15 min) with and without release (1 hr) served as a model for comparative regional studies of synaptosomal 3H-5-hydroxytryptamine (3H-5-HT) uptake and release in adult and young gerbils. A decreased uptake and an increased release of 5-HT was observed in the adult after ischemia alone and/or ischemia with reflow. At the same time, 5-HT uptake was not affected except in the cortex and the release was reduced in the young. These findings indicate that the same ischemic insults affect differently the synaptosomal uptake and/or release of 5-HT in adult and young brain.
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PMID:Effect of cerebral ischemia on synaptosomal uptake and release of 3H-5-hydroxytryptamine in adult and young Mongolian gerbils. 233 47

Idebenone, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, at a dose of 100 mg/kg (i.p.) markedly increased the level of 5-hydroxyindole-3-acetic acid (5-HIAA) in several brain regions without affecting monoamine contents in normal rats. In rats with cerebral ischemia, idebenone (10 mg/kg, i.p.) normalized the decreased levels of 5-HIAA in the cerebral cortex, hippocampus, diencephalon and brain stem. A 5-hydroxytryptamine (serotonin, 5-HT) biosynthesis inhibitor, DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) decreased the levels of 5-HT to one-third of the control level 24 h after administration. Idebenone (10, 30, or 100 mg/kg, i.p.), administered 24 h after the treatment with PCPA, accelerated the PCPA-induced 5-HT decreased in the hippocampus, diencephalon and brain stem in a dose-dependent manner. Idebenone (100 mg/kg, i.p.) stimulated the release of 5-HT in the dorsal hippocampus as determined by in vivo differential pulse voltammetry. Idebenone, like p-chloroamphetamine (PCA), stimulated 5-HT release from slices of hippocampus and diencephalon, and the formation of cyclic AMP in a concentration-dependent manner in rat diencephalon slice. This stimulation was almost completely blocked by methysergide, a 5-HT receptor blocker. Idebenone slightly and PCA markedly inhibited 5-HT uptake into hippocampus slices. The mechanism of the 5-HT releasing actions of idebenone in the hippocampal slices may be mediated through endogenous calcium. These results suggest that idebenone has an enhancing effect on the turnover of 5-HT in the hippocampus, diencephalon, and brain stem of rats.
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PMID:Effects of idebenone on metabolism of monoamines and cyclic AMP formation in rats. 247 75

The effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the contents, turnover, release and uptake of monoamines, especially serotonin (5-HT), in various brain regions of Wistar rats were studied in vivo and in vitro. In normal rats, an intraperitoneal (i.p.) dose of 100 mg/kg of CV-2619 had no significant effect on the levels of norepinephrine (NE), dopamine (DA) and their metabolites, and 5-HT in the brain regions examined, but it increased the levels of 5-hydroxyindole-3-acetic acid (5-HIAA), the main metabolite of 5-HT, in many brain regions. In rats with cerebral ischemia, a low dose (10 mg/kg, i.p.) of CV-2619 normalized the decreased levels of 5-HIAA in the cerebral cortex, hippocampus, diencephalon and brain stem. A 5-HT biosynthesis inhibitor, DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.), decreased the levels of 5-HT in all brain regions to one-third of the control levels 24 hr after administration in normal rats. CV-2619 (10, 30 or 100 mg/kg, i.p.), administered 24 hr after the treatment with PCPA, accelerated the PCPA-induced 5-HT decreases in the hippocampus, diencephalon and brain stem in a dose-dependent manner. In vitro CV-2619, like p-chloroamphetamine (PCA), stimulated 5-HT release from slices of the hippocampus and diencephalon. CV-2619 slightly inhibited and PCA markedly inhibited 5-HT uptake into hippocampal slices. The mechanism of the 5-HT releasing action of CV-2619 in hippocampal slices seems to be mediated through endogenous calcium. These results suggest that CV-2619 has an enhancing effect on the turnover of 5-HT in the hippocampus, diencephalon and brain stem of rats.
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PMID:Effects of idebenone (CV-2619) on metabolism of monoamines, especially serotonin, in the brain of normal rats and rats with cerebral ischemia. 258 71

30 min of low flow cerebral ischaemia (0.12 ml/min) was imposed on normal and hyperglycaemic rats. Some were allowed to recover for up to 10 h. Whole tissue homogenates, or synaptosomes from the brains of each group were examined for content of noradrenaline, dopamine and 5-HT of defined anatomical regions. In normoglycaemic rats immediately after ischaemia there was a significant reduction in the content of all three neurotransmitters in cortex, striatum and hippocampus but not in diencephalon (except possibly 5H-T) or brain stem. The amounts of all three neurotransmitters returned to control values after about 30 min reperfusion and remained so for 10 h. By contrast, no changes in neurotransmitter levels were found either during or after ischaemia in hyperglycaemic rats. Dopamine synthesis rates in the striatum were increased after ischaemia and returned to control levels in 2-3 h in normoglycaemic rats but were unaltered in hyperglycaemic animals. Binding sites for spiroperidol and LSD were compared in cortical synaptosomes and whole cortex homogenates in the presence and absence of agonists and antagonists. Both types of membrane showed similar binding properties and there was no significant change in number or character of binding sites immediately following ischaemia or during 10 h of brain reperfusion. The significance of these findings is discussed in relation to ischaemic brain damage.
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PMID:Some effects of ischaemia and hyperglycaemia on neurotransmitter metabolism in rat brain. 286 56


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