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Query: UMLS:C0038454 (stroke)
 147,016 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

It has been hypothesized that acute lesions of the brain enlarge through an autodestructive process. Serotonin (5HT), a potent cerebral vasoconstrictor, is believed by some to mediate the process by reducing cerebral blood flow (CBF) in tissue surrounding the lesion. The hypothesis was tested in cynomologus monkeys anesthetized with ketamine and nitrous oxide. Craniectomies, 7 mm in diameter, were performed in each parietal area. The dura was opened and polarographical electrodes of thin platinum wire were inserted into the parietal lobe cortex of each hemisphere. Mock cerebrospinal fluid (CSF) was irrigated continously onto the brain surrounding the electrodes, from which local CBF was determined repeatedly by the hydrogen-clearance technique. After baseline CBF was established, solutions of 5HT in mock CSF (in concentrations of 5 X 10(-7) M, 5 X 10(-5) M, and 5 X 10(-3) M) were irrigated onto one hemisphere while the opposite hemisphere served as control. 5HT failed to change CBF. Although 5HT is a potent vasoconstrictor, under physiologic conditions it apparently is unable to effect hemodynamically significant constriction of the peripheral cerebral vasculature of the anesthetized monkey brain.
Stroke
PMID:Effect of topically applied serotonin on local cerebral blood flow. 41 85

In MAO-inhibited dogs, 5-hydroxytryptophan (5-HTP), either 5 or 10 mg/kg i.v., caused hypotension with variable effects on heart rate. Reflex responses to bilateral carotid artery occlusion (BCO) were greatly inhibited by 5-HTP. The hypotensive effects were markedly inhibited by cerebral and extracerebral decarboxylase inhibition with RO 4-4602 and the inhibition of BCO was delayed. Selective extracerebral decarboxylase inhibitation with MK 486 did not prevent either the hypotensive action of 5-HTP or the effect on BCO, although the amino acid now consistently caused bradycardia. Left ventricular pressure and dP/dt were reduced, but cardiac output was maintained by an increase in stroke volume. Hypotension was due predominantly to decreased peripheral resistance. The hypotensive action of 5-HTP was abolished or greatly attenuated after pretreatment with either yohimbine or methysergide, but was unaffected by haloperidol. These results indicate that cerebral decarboxylation and formation of 5-HT are responsible for the hypotension after 5-HTP in MAO inhibited dogs.
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PMID:Centrally-mediated cardiovascular effects of 5-hydroxytryptophan in MAO-inhibited dogs: modification by autonomic antagonists. 108 42

Arteriolar responses were measured on the cerebral surface of the mouse using an image splitter and TV monitor. The response to locally applied norepinephrine (NOR) was significantly more frequent for vessels greater than 30 mu I.D. than for smaller vessels. However, even the smaller vessels were frequently constricted by NOR in doses of 5 mug per milliliter. Reserpine (5 mg per kilogram) failed to alter the response to NOR at either 24 or 72 hours after reserpinization. At 48 hours the threshold dose of NOR was reduced, but the effect was slight (two-tailed, P = 0.08). Both propranolol (10(-6) M3 and phentolamine (10(-5M) blocked responses to 5 mug per milliliter of NOR, but neither agent altered resting arteriolar diameter. Isoproterenol, tyramine, and histamine had no effect. Serotonin (5HT) constricted the arterioles but did not potentiate the response to NOR. Additive or potentiated effects were not observed with NOR 5HT or histamine in any combination. These data indicate the presence of alpha-adrenergic receptors in murine cerebral surface arterioles, but do not establish a significant tonic effect of norepinephrine. The existence or role of a beta-receptor in these murine cerebral surface arterioles remains an unsettled question.
Stroke
PMID:Pial arteriolar responses in the mouse brain revisited. 127 7

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.
Stroke 1990 Dec
PMID:Platelets as a source of vasoactive mediators. 212 87

Serotonin (5-HT) uptake into platelets is reduced in functionally depressed patients. Depression following stroke (cerebrovascular accident; CVA) is common and severe. Sixteen patients who had suffered a CVA within 6 to 12 months and who were medication-free had blood taken for measurement of platelet 5-HT uptake. Seven of these patients were depressed. These were compared with age- and sex-matched hospital controls. No difference in platelet 5-HT uptake was found across these groups.
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PMID:Platelet 5-HT uptake in post-stroke depression. 239 28

The number of platelets and their content in serotonin (5-HT) were determined in 12-week-old spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and in normotensive Wistar-Kyoto rats (WKY). Spontaneously hypertensive rats had 49% more platelets and a 65% higher platelet 5-HT circulating pool than SHRSP and WKY. An increased synthesis of 5-HT by enterochromaffin cells in SHR is suggested by the lower level of plasma total and albumin-bound tryptophan and by the higher free/bound tryptophan ratio found in those rats, as compared with WKY. In SHRSP, a decrease of platelet survival time was reported, associated to an increased platelet production. This would explain the absence of variation of platelet number and 5-HT content.
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PMID:Platelet serotonin and blood tryptophan in spontaneously hypertensive and normotensive Wistar-Kyoto rats. 241 39

Pulmonary embolism may cause pulmonary hypertension by mechanical obstruction, which might be amplified by vasoconstriction induced by serotonin released from the emboli. The purpose of the present study was to examine whether 5-HT2-receptors are involved in serotonin-induced pulmonary hypertension. Ketanserin was used as 5-HT2-serotonergic antagonist. In nine anesthetized mongrel dogs, the effect of serotonin infusions (10, 50, 100 micrograms/kg . min) on mean pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), cardiac output (CO), stroke volume (SV), cardiac contractility (dP/dtmax), heart rate (HR), and mean aortic pressure (PAO) was studied with and without treatment by ketanserin (20 and 100 micrograms/kg). Serotonin caused dose-dependent increase in PAP, PVR, CO, SV, and dP/dtmax. A dose of 20 micrograms/kg ketanserin did not affect hemodynamics significantly, whereas 100 micrograms/kg of the compound significantly reduced PAO, TPR, and left ventricular dP/dtmax. The serotonin-induced increases in PAP, PVR, dP/dtmax, CO, and SV were reduced significantly by 100 micrograms/kg ketanserin; the lower dose of ketanserin had only a slight blocking effect. Ketanserin blocks serotonin-induced pulmonary vasoconstriction partly, but it seems also to antagonize the positive inotropic effect of the monoamine.
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PMID:Effects of serotonin on the cardiopulmonary circulatory system with and without 5-HT2-receptor blockade by ketanserin. 241 62

Ketanserin, a selective serotonergic (5-HT2) antagonist, also has affinity for alpha 1-adrenoceptors. It is not clear whether the hypotensive mechanism of ketanserin is due to its antagonistic action to 5-HT2 receptor or to its affinity for alpha 1 adrenoceptors. The hypotensive mechanism of ketanserin was studied in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anesthetized rats were used (alpha-chloralose + urethane, i.p.). Up to 3 ml of blood was drawn from each rat for analysis. Plasma norepinephrine (NE) was determined by radioenzymatic assay. Plasma serotonin (5-HT) was determined by HPLC-ECD. Adrenal nerve discharges were counted by a digital pulse counter. Ketanserin (0.5 mg/kg, 5.0 mg/kg, i.v.) produced a dose-dependent reduction of mean arterial pressure (MAP) in both SHRSP and WKY. MAP of SHRSP decreased significantly as compared with WKY. Both plasma NE and 5-HT showed a tendency to increase during ketanserin administration (5.0 mg/kg, i.v.). Ketanserin significantly antagonized the BP response induced by exogenously injected 5-HT (30 micrograms/kg) and NE (10 micrograms/kg). Adrenal nerve activity was reduced in parallel with the decrease in BP and HR. These findings suggest that ketanserin produced a decrease in BP via both peripheral and central action in rats.
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PMID:[Effect of ketanserin on blood pressure in rats]. 241 29

Blood proteins could play a critical role in the pathogenesis of cerebral vasospasm in subarachnoid hemorrhage (SAH) as agonists and as antagonists of vasoconstriction. The present study was designed primarily to quantify the inhibition produced by antithrombin III of the phasic responses elicited by cumulative doses of KCl, serotonin (5-HT), uridine triphosphate (UTP), and thrombin in isolated canine basilar arteries, and to ascertain whether other proteins might act similarly. Antithrombin III (1 unit/ml and 3 units/ml) given 2 min beforehand inhibited all agonists. The inhibition was not dependent on a functional endothelium nor due to stimulation of the electrogenic sodium pump. Alpha2-macroglobulin (0.1 mg/ml and 0.4 mg/ml) inhibited the contractile responses to high K+, 5-HT and thrombin. Kallikrein (1 and 4 units/ml) did not inhibit UTP but inhibited high K+ and 5-HT through an effect on the endothelium. Kallikrein (1 unit/ml) irreversibly blocked the responses to thrombin. Globulins (3 mg/ml) and fibrinogen (0.3 mg/ml) were not inhibitory. The results demonstrate that anticoagulant proteins are very effective nonspecific inhibitors of the vasoconstriction, whereas the serine protease kallikrein selectively blocks thrombin. The remarkable potency of antithrombin III suggests that it may protect cerebral arteries from exhibiting vasospasm in SAH.
Stroke
PMID:Vasodilator proteins: role in delayed cerebral vasospasm. 242 60


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