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

We conducted the present study to investigate the effects of 5-hydroxytryptamine agonists on brain morphology after the induction of focal cerebral ischemia by permanent occlusion of the left middle cerebral artery in rats and mice. Forty-eight hours after vessel occlusion, the damage was quantified in rats by planimetry and subsequent integration on cresyl violet-stained serial sections and in mice by planimetric analysis of the damaged cortical surface after counterstaining with carbon black. All 5-HT1A agonists investigated substantially decreased cortical infarct size in the rat focal ischemia model (p less than 0.05). Drugs were applied 30 minutes before the induction of ischemia, and efficacy was demonstrated for 8-OH-DPAT (1 mg/kg s.c.), buspirone (10 mg/kg i.p.), gepirone (10 mg/kg i.p.), ipsapirone (10 or 30 mg/kg i.p.), and Bay R 1531 (1 mg/kg i.p.). The most pronounced effects were seen with the higher dose of ipsapirone and Bay R 1531, both compounds reducing cortical infarct size by more than 60%. Except for 8-OH-DPAT, the 5-HT1A agonists also caused a reduction in total infarct volumes. In a separate series, ipsapirone (30 mg/kg i.p.), applied 1 hour after vessel occlusion, led to a reduction in cortical and total infarct volumes by about 50% compared with corresponding controls (p less than 0.05). In neither series was striatal damage influenced. We tested the compounds in the mouse ischemia model over a broad dose range.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1990 Dec
PMID:5-hydroxytryptamine1A agonists. A new therapeutic principle for stroke treatment. 214 35

The activation of 5-hydroxytryptamine receptors exerts an inhibitory influence on neuronal activity in a way similar to the activation gamma-amino-n-butyric acid and adenosine A1 receptors. Therefore, we hypothesized that 5-HT1A-receptor agonists might exert a neuroprotective effect. We tested the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil. Ipsapirone protected 53% of pyramidal neurons (p less than 0.05) in the CA1 area of the hippocampus from ischemic damage at a dose of 3 mg/kg. Bay R 1531 showed a powerful neuroprotective effect with 100% preservation of neurons at a dose of 3 mg/kg (p less than 0.001) while gepirone and 8-OH-DPAT were ineffective. These findings suggest that 5-HT1A-receptor agonists might be effective tools for the therapy of cerebral ischemia. However, the varying results indicate that transient forebrain ischemia in the gerbil may not be the optimal model system to demonstrate clearly the neuroprotective activity of these compounds.
Stroke 1990 Dec
PMID:Effects of 5-hydroxytryptamine1A-receptor agonists on hippocampal damage after transient forebrain ischemia in the Mongolian gerbil. 214 36

The laterofrontal (LF) cirri on isolated gill filaments of Mytilus edulis, prepared in natural seawater, are active and initially beat with an average frequency of about 8 Hz (with a range of 6-14 Hz). However, the lateral (L) cilia on these filaments are arrested in a position at the end of their recovery stroke. Perfusion of the filament with artificial seawater (ASW), with or without 1% ethanol, has little or no biological effect on the activity of the LF cirri, although a transitory decrease in frequency often accompanies the perfusion process. The L cilia remain arrested during perfusion with ASW. The exposure of the gill to low levels of 5-hydroxytryptamine (5HT) (10(-8) less than 5HT less than 10(-7) M) has no effect on the activity of the LF cirri but stimulates the L cilia to beat. Exposure to higher concentrations of 5HT (greater than 10(-7) M) elevates the beat frequency of the L cilia and simultaneously inhibits the activity of the LF cirri, leading to their arrest in a position at the end of the effective stroke. This arrest of the LF cirri occurs as the L cilia attain a 5HT-induced beat frequency between 12 to 14 Hz. The influence of 5HT on the L cilia and the LF cirri can be reversibly mimicked or enhanced by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). A concentration of 0.5 mM IBMX mimics low 5HT concentrations (about 10(-7) M) by stimulating the L cilia to beat without affecting the beat frequency of the LF cirri. A combination of 10(-7) M 5HT and 0.5 mM IBMX in ASW mimics high (greater than 10(-6) M) 5HT concentrations by arresting the LF cirri and increasing the beat frequency of the L cilia. Under these conditions, the threshold of the LF cirri arrest response is again found to occur as the L cilia attain a beat frequency of 12-14 Hz. These results suggest that the mechanisms of LF cirri arrest and L cilia activation are mediated by 5HT-induced changes in intracellular cyclic AMP levels.
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PMID:The antagonistic effects of 5-hydroxytryptamine and methylxanthine on the gill cilia of Mytilus edulis. 241 3

We devised the present experiments to assess the effects of ischemia on the production of dopamine in the caudate nucleus of spontaneously hypertensive stroke-resistant rats. Ringer's solution was continuously perfused at a rate of 10 microliters/min through 0.2-mm-diameter dialysis tubing implanted in the rat's caudate nucleus. After bilateral occlusion of the common carotid artery, perfusate was collected at 20-minute intervals for 120 minutes and was analyzed for monoamines and their metabolites using high-performance liquid chromatography and an electrochemical detection system. The extracellular concentration of dopamine increased abruptly approximately 3 minutes after the ischemic insult, reached a maximum at between 20 and 40 minutes after the insult, and subsequently decreased. During the 120 minutes, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindole-3-acetic acid concentrations decreased significantly, whereas 5-hydroxytryptamine was not detected. Our results indicate that during cerebral ischemia a large increase in extracellular dopamine concentration in the caudate nucleus occurs, probably as a result of energy failure of the cell membranes. This leakage of dopamine may be a causal factor in the neuronal damage associated with cerebral ischemia.
Stroke 1988 Dec
PMID:Striatal dopamine in acute cerebral ischemia of stroke-resistant rats. 246 90

An isometric tension measurement of ring segments was performed in the rabbit basilar and common carotid arteries in vitro to investigate the regional differences in the calcitonin gene-related peptide (CGRP)-induced vasodilation and the effect of subarachnoid hemorrhage on CGRP-induced vasodilation. CGRP elicited vasodilation of the rabbit basilar artery in a dose-dependent fashion when the artery was precontracted by 10(-5) M 5-hydroxytryptamine, whereas almost no relaxation occurred in the rabbit common carotid artery. The relaxation of the basilar artery was 64.03 +/- 1.85% at 3 x 10(-8) M CGRP, with an EC50 of 8.46 +/- 0.08. Two days after experimental subarachnoid hemorrhage, CGRP-induced relaxation of the rabbit basilar artery was 53.96 +/- 8.08% of the 10(-5) M 5-hydroxytryptamine-induced contraction, not significantly different from that of the basilar artery of the control rabbit. Our findings suggest that CGRP induces potent vasodilation in the rabbit basilar artery and that no impairment of vasodilation occurred after experimental subarachnoid hemorrhage. We speculate that CGRP may have therapeutic potential in cerebrovascular disease such as vasospasm after subarachnoid hemorrhage.
Stroke 1989 Jan
PMID:Effect of subarachnoid hemorrhage on calcitonin gene-related peptide-induced relaxation in rabbit basilar artery. 278 99

We examined the effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger and an inhibitor of ischemia-induced brain edema, on monoamine metabolism in the brains of both normal and ischemic rats. In normal rats, 3 mg/kg i.v. MCI-186, a dose that prevents ischemic brain edema, had no significant effect on brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or their metabolites. After the injection of 5 microliters of 3% polyvinyl acetate into the left internal carotid artery, concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid markedly increased, but that of norepinephrine decreased, in the left telencephalon of embolized rats compared with control rats injected with vehicle; the concentration of 5-hydroxyindoleacetic acid also increased slightly. These effects were maximal 2 hours after embolization. The turnover rate of dopamine between 6 and 8 hours after embolization was significantly higher but that of norepinephrine was slightly lower than that in vehicle-treated rats. When rats were treated with 3 mg/kg i.v. MCI-186 immediately after the injection of polyvinyl acetate, the embolization-induced changes in monoamine metabolism were less marked. Our results suggest that MCI-186 attenuates ischemia-induced changes in brain monoamine metabolism, probably due to its free radical scavenging action, although it has no marked effect in normal rats.
Stroke 1989 Nov
PMID:Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain. 281 91

The stainless steel cannula inserting method was used to investigate the blocking effects of nimodipine on vascular responses to intraluminal administration of 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) before and after application of abluminal blood containing thrombin in isolated and perfused canine basilar arteries. A transient elevation of perfusion pressure was observed initially, and during the course of the experiment the perfusion pressure gradually increased. Nimodipine significantly depressed both transient and prolonged changes of perfusion pressure. Dose-dependent vasoconstriction induced by 5-HT was significantly enhanced, while that evoked by KCl was significantly attenuated for up to 8 hours after the application of blood. Pretreatment with nimodipine inhibited vasoconstriction to 5-HT less effectively than to KCl both before and after application of blood. The proportion of the 5-HT-induced vasoconstriction, which was sensitive to nimodipine, was reduced after application of blood, while no such change was observed in the responses to KCl. It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage of subarachnoid hemorrhage may be mediated mainly by changes in intracellular calcium utilization rather than by the increase of calcium influx through nimodipine-sensitive channels.
Stroke 1989 Jan
PMID:Effect of nimodipine on canine cerebrovascular responses to 5-hydroxytryptamine and potassium chloride after exposure to blood. 291 23

To determine whether extraluminal or intraluminal hemoglobin inhibits endothelium-dependent relaxation, we measured the vascular responsiveness of rabbit basilar artery in an in vitro perfusion system and we performed immunohistochemical staining for hemoglobin. In the in vitro study, we applied agents from either the intraluminal or the extraluminal side of excised basilar arteries. KCl-induced contraction was the same with either application. Acetylcholine-induced maximal relaxations were 57.6 +/- 8.5% of the contraction induced by 10(-5) M 5-hydroxytryptamine for control, 3.3 +/- 0.3% for intraluminal, and 34.9 +/- 8.6% for extraluminal applications. Adenosine triphosphate-induced maximal relaxations were 64.2 +/- 4.1% of the contraction induced by 10(-5) M 5-hydroxytryptamine for control, 26.9 +/- 3.8% for intraluminal, and 42.2 +/- 6.0% for extraluminal applications. Hemoglobin's inhibition of acetylcholine- and adenosine triphosphate-induced relaxation was significantly greater with intraluminal than with extraluminal application (p less than 0.05). The immunohistochemical study revealed hemoglobin in the outer layer of the smooth muscle and in the adventitia when 10(-5) M hemoglobin was applied extraluminally for 5 minutes, whereas hemoglobin was observed on the surface of the endothelial cells after intraluminal application. Our findings suggest that hemoglobin inhibits acetylcholine- or adenosine triphosphate-induced relaxation by binding to endothelium-derived relaxing factor (EDRF) and by inhibiting production of EDRF. Hemoglobin's inhibitory effect on endothelium-dependent relaxation may be important in the pathogenesis of vasospasm after subarachnoid hemorrhage.
Stroke 1988 Dec
PMID:Comparison of intraluminal and extraluminal inhibitory effects of hemoglobin on endothelium-dependent relaxation of rabbit basilar artery. 326 26

The endothelium-dependent and presumed endothelium-independent vasodilators acetylcholine and sodium nitroprusside, respectively, were used to characterize relaxation responses of mesenteric resistance arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Vessels were preconstricted using concentrations of norepinephrine or 5-hydroxytryptamine, which reduced their diameters by 50 to 60%. Relaxation responses to acetylcholine (10(-8) - 10(-7) M) were significantly smaller (p less than 0.05) in vessel segments from SHRSP, but the maximal relaxations at higher concentrations were the same in both strains. However, SHRSP vessels relaxed to a greater extent than did those of the WKY at all concentrations of sodium nitroprusside. Endothelium removal significantly enhanced sodium nitroprusside-induced dilations in both rat strains, and the dilations were significantly greater in segments from SHRSP in the concentration range of 3 X 10(-8) to 10(-6) M. The decreased relaxation to acetylcholine in resistance arteries from adult hypertensive rats compared with those from the normotensive strain suggests that functional alterations in the endothelium may play a role in hypertensive disease.
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PMID:Endothelium-dependent and endothelium-independent vasodilation in resistance arteries from hypertensive rats. 336 77

We evaluated the effects of aging and hypertension on endothelium-dependent relaxation of rat common carotid arteries using 14-week-old (young) and 11-month-old (old) Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). Isometric tension of common carotid artery ring segments was measured. With a resting tension of 2.0 g determined from the baseline tension-contraction curves, precontraction was induced by 10(-5) M 5-hydroxytryptamine and endothelium-dependent relaxation was measured by application of either acetylcholine or adenosine 5'-triphosphate (ATP). Mean arterial blood pressure was 73.1 +/- 3.0 mm Hg in WKY and 110.0 +/- 3.1 mm Hg in SHR. These baseline values were significantly different. Acetylcholine-induced maximal relaxations were 70.1 +/- 2.6% of the 5-hydroxytryptamine-induced contraction in young WKY, 45.6 +/- 2.1% in old WKY, 35.1 +/- 1.8% in young SHR, and 21.4 +/- 2.5% in old SHR. On the other hand, ATP-induced relaxations were 52.0 +/- 3.2%, 35.7 +/- 3.8%, 21.7 +/- 3.5%, and 17.0 +/- 1.8% in the groups, respectively. Acetylcholine-induced relaxations were significantly different between WKY and SHR, young and old, independently. On the other hand, ATP-induced relaxations were also significantly different between young and old WKY, although no significant difference was observed between young and old SHR. The fact that endothelium-dependent relaxation of a cephalic artery is impaired in old rats and in hypertensive rats suggests that aging and hypertension are risk factors that may augment the disturbance of the cerebral circulation in pathologic conditions.
Stroke 1988 Jul
PMID:Effects of aging and hypertension on endothelium-dependent vascular relaxation in rat carotid artery. 338 60


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