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

The effects of citalopram, a serotonin (5-HT) reuptake inhibitor, on cerebral blood flow (CBF) and concentration of 5-HT and its metabolite were investigated in spontaneously hypertensives rats (SHR) subjected to forebrain ischemia. Cerebral ischemia was induced by bilateral carotid artery occlusion. The concentration of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), increased during cerebral ischemia in most brain regions examined, while that of 5-HT increased only in the frontal cortex and the striatum. Citalopram restored the 5-HIAA concentrations to the preischemic normal levels. Citalopram had no effect on the cortical CBF, before and during ischemia. These results suggest that citalopram attenuates ischemia-induced hypermetabolism of 5-HT in the brain. The effects of citalopram are independent of hemodynamic factors including cerebral blood flow, and are likely to be mediated by a direct inhibition of the neuronal 5-HT reuptake system.
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PMID:Citalopram, a serotonin reuptake inhibitor, and brain ischemia in SHR. 755 75

The release of neurotransmitters principally glutamate during cerebral ischemia has been extensively studied. It is well recognized that ischemia induced release of glutamate plays a key role in "excitotoxic" neuronal death. The role of monoaminergic neurotransmitters is however unclear. The purpose of this study was to evaluate the extracellular norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and serotonin (5-HT) under varied degrees of ischemia in the acute focal ischemic model of the human brain by in-vivo microdialysis. The ischemic response of these amines was correlated with the glutamate levels. Our study concludes that these amines and metabolites can be detected in the human "stroke" model. No marked fluctuations were noted in the levels of norepinephrine and DOPAC. However, significant changes to partial and total ischemia were noted in the extracellular levels of 5-HIAA and 5-HT. These compounds showed a dramatic increase with the onset of ischemia with higher detectable levels in the partial ischemic state in comparison to the total ischemic dialysate levels. The exact role played by the differential increase in the levels of 5-HT to the other catecholamines in the pathogenesis of ischemic neuronal damage remains unclear and warrants further study.
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PMID:Evaluation of monoaminergic neurotransmitters in the acute focal ischemic human brain model by intracerebral in vivo microdialysis. 872 64

Stimulation of the 5-HT2A receptors by serotonin has been reported to exert an excitatory effect on neocortical neurons in rats and mice, to facilitate ischaemia-induced release of excitatory amino acids and to mediate the vasomotor constrictor component of the response of blood vessels to 5-HT. 5-HT2A receptor antagonists have, therefore, been proposed as potential protectants against the effects of cerebral ischaemia. The aim of this study was to evaluate the effects of two relatively selective 5-HT2A receptor antagonists, ketanserin and ritanserin, on delayed hyperactivity and the ensuing neuronal degeneration induced by 3 minutes of bilateral carotid artery ligation in Mongolian gerbils. Effects were compared to that of flunarizine, which blocks calcium overload and served as a positive control in this paradigm. Temporal and/or rectal temperatures were measured and strictly controlled during the ischaemia and the early reperfusion phase. Locomotor activity was measured one day after the ischaemia and neuronal degeneration quantified 7 days later using an image analysis system (Quantimet 570, Leica). Global ischaemia in gerbils elicits hyperactivity associated with a delayed neuronal degeneration predominantly in the CA1 zone of the hippocampus. Ketanserin and ritanserin (3 and 10 mg/kg ip, twice daily for 3 days, pre- and postischaemia) did not protect the CA1 neurons against ischaemic damage. The postischaemic hyperactivity was inhibited only with the higher dose of ketanserin. As previously reported, flunarizine (30 mg/kg po) markedly reduced neuronal degeneration (-44.2%, p < 0.01) and totally abolished the ischaemia-induced hyperactivity. These data demonstrate that ketanserin and ritanserin are not effective protectants of the gerbil hippocampus against ischaemic damage when the body temperature of the animals is controlled, thus suggesting that 5-HT2A receptors are not directly implicated in the pathogenesis of global cerebral ischaemia in this model.
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PMID:Lack of efficacy of 5-HT2A receptor antagonists to reduce brain damage after 3 minutes of transient global cerebral ischaemia in gerbils. 880 77

To clarify the serotonergic mechanisms involved in the protection against ischemic neuronal damage, ZD-211 (citalopram HBr), a serotonin (5-hydroxytryptamine; 5-HT) re-uptake inhibitor, or buspirone, a 5-HT1A agonist, was locally administered into the hippocampus of gerbils. Additionally, to clarify the role of the 5-HT nervous system in the hippocampus during ischemic neuronal damage, animals were subjected to the local administration of 5,7-dihydroxytryptamine (5,7-DHT), a 5-HT neurotoxin, before ischemia challenge. Gerbils received intrahippocampal administration of ZD-211 (200 nmol/animal) or buspirone (20 nmol/animal) before 5-min ischemia. 5,7-DHT was intrahippocampally administered 7 days before a 2-min non-lethal ischemia challenge. In vehicle-treated animals subjected to 5 min of ischemia, almost all hippocampal CA1 pyramidal neurons were lost. The treatment with ZD-211 or buspirone showed a significant protective effect, and the number of neurons was significantly increased compared to vehicle-treated animals. Pretreatment with NAN-190, a 5-HT1A antagonist, completely abolished the protective effect of ZD-211 or buspirone. In the 5,7-DHT-treated animals, the number of neurons was significantly reduced following 2 min of ischemia compared to vehicle-treated animals in which this period of ischemia is non-lethal. Thus, intrahippocampal treatment with ZD-211 or buspirone can protect neuronal damage following transient ischemia in gerbils. These effects of ZD-211 and buspirone were mediated through the 5-HT1A receptor in the hippocampus. Furthermore, the destruction of the 5-HT nervous system in the hippocampus aggravated ischemic neuronal damage. Therefore, this study showed that the enhanced activity of the 5-HT nervous system in the hippocampus may protect against neuronal damage following cerebral ischemia.
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PMID:Role of hippocampal serotonergic neurons in ischemic neuronal death. 906 88

The patch-clamp technique was applied in out-side-out patches of N1E-115 mouse neuroblastoma cells to investigate the effects of ifenprodil [(+/-) erythreo-ifenprodil tartratel, a drug with neuroprotective properties in cerebral ischemia, on the inward currents through 5-HT3 receptor channels. A high time resolution was achieved by using a rapid solution exchange system (exchange rate <1 ms). Ifenprodil inhibited the peak currents evoked by 30 microM 5-HT in a concentration-dependent but voltage-independent manner. The effect was most potent when ifenprodil was continuously applied to the patches 45 s before and during the 2-s administration of 5-HT (IC50=16 microM) and it was only slightly less potent when it was applied during the 45 s prior to 5-HT only (IC50=29 microM). When applied in this manner, ifenprodil also produced a concentration-dependent increase of the onset time constant (tauON) of the 5-HT (30 microM)-induced currents. When the drug was exclusively co-applied with 5-HT, ifenprodil was least potent in inhibiting the peak currents (IC50=98 microM), and it had no effect on the current onset kinetics. All protocols of ifenprodil application accelerated current inactivation as reflected by a decrease of the current inactivation time constant (tauOFF). All effects of ifenprodil were reversible after washout periods of 2-5 min. In conclusion, the potency of ifenprodil in inhibiting the inward current through 5-HT3 receptor channels is strongly dependent on the application protocol: presence of the drug before the agonist-induced activation of the 5-HT3 receptor channels is necessary for a relatively potent inhibition of the 5-HT-induced peak current and is a prerequisite for the prolongation of tauON; in addition, a weak but fast inhibitory effect on the current amplitude and decay constant of the 5-HT-induced current was revealed by the experiments in which ifenprodil was exclusively present during exposure to 5-HT. Three alternatives compatible with the components of the ifenprodil effect have been discussed: (1) different effects of the two enantiomers, (2) action via two different mechanisms, and (3) operation via a single mechanism only.
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PMID:Inhibition of 5-HT3 receptor cation channels by ifenprodil in excised patches of N1E-115 cells. 974 98

Reactivity of the middle cerebral artery (MCA) to serotonin was attenuated in vitro in vessels taken from rats following an audiogenic stress. The MCA reactivity to endothelin remained unchanged. Chronic cerebral ischemia diminished the 5-HT-induced contraction and the contractile responses to endothelin were enhanced. Preliminary hypoxic adaptation decreased the artery sensitivity to endothelin in ischemic animals. The findings suggest that a progressing ischemia may involve changes in reactivity of cerebral vessels whereupon hypoxic adaptation may prove to be protecting the brain from ischemia development.
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PMID:[Changes in reactivity of the middle cerebral artery caused by cerebral circulation disturbances of ischemic and hemorrhagic types in rats]. 980 79

This study attempted to ascertain whether the ischemic damage to neurons and monoamine overload in brain that occur during rat heatstroke can be attenuated by heat shock protein (HSP) 72 induction. Effects of heatstroke on mean arterial pressure (MAP), cerebral blood flow (CBF), brain dopamine (DA) and serotonin (5-HT) release, and neural damage score were assayed in rats 0, 16, or 48 h after heat shock (42 degrees C for 15 min) or chemical stress (5 mg/kg sodium arsenite ip). Brain HSP 72 in rats after heat shock or chemical stress was detected by Western blot, and brain monoamine was determined by a microdialysis probe combined with high-performance liquid chromatography. Heatstroke was induced by exposing the animal to a high ambient temperature (43 degrees C); the moment at which MAP and CBF decreased from their peak values was taken as the time of heatstroke onset. Prior heat shock or chemical stress conferred significant protection against heatstroke-induced hyperthermia, arterial hypotension, cerebral ischemia, cerebral DA and 5-HT overload, and neural damage and correlated with expression of HSP 72 in brain at 16 h. However, at 48 h, when HSP 72 expression returned to basal values, the above responses that occurred during the onset of heatstroke were indistinguishable between the two groups (0 h vs. 48 h). These results lead to the hypothesis that the brain can be preconditioned by thermal or chemical injury, that this preconditioning will induce HSP 72, and that HSP 72 induction will correlate quite well with anatomic, histochemical, and hemodynamic protection in rat heatstroke.
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PMID:Heat shock protein expression protects against cerebral ischemia and monoamine overload in rat heatstroke. 1036 76

The aim of this study was to investigate the effect of 30 min forebrain ischemia, followed by 120 min reperfusion on extracellular fluid (ECF) levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of gerbils, so as to obtain further information on the mechanism of Radix Salviae Miltiorrhizae (RSM)-induced neuroprotection. Microdialysis was used to sample the extracellular space. Dialysate was measured by high performance liquid chromatography with electrochemical detector (HPLC-ED). ECF DA, NE levels increased from basal levels by 282, 227 and 221 folds, by 9.14, 8.51 and 8.25 folds, respectively for the three ischemic duration (0-10; 11-20; 21-30 min). ECF DA, NE, 5-HT levels in the RSM-treated group were significantly decreased as compared with those in the control group during ischemia (P < 0.01). The results suggested that monoamine neurotransmitters were involved in ischemic neuron damage directly or indirectly; and that RSM plays a protective role during cerebral ischemia by attenuating the dysfunctions of monoamine neurotransmitters.
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PMID:Effects of transient forebrain ischemia and radix Salviae miltiorrhizae (RSM) on extracellular levels of monoamine neurotransmitters and metabolites in the gerbil striatum--an in vivo microdialysis study. 1068 74

The serotonin (5-HT)(1A) receptor agonists have already been shown to protect cultured neurons from excitotoxic as well as from apoptotic damage [B. Ahlemeyer, J. Krieglstein, Stimulation of 5-HT(1A) receptors inhibits apoptosis induced by serum deprivation in cultured neurons from chick embryo, Brain Res. 777 (1997) 179-186. ; B. Ahlemeyer, A. Glaser, C. Schaper, I. Semkova, J. Krieglstein, The 5-HT(1A) receptor agonist, Bay x 3702, inhibited apoptosis induced by serum deprivation in cultured neurons, Eur. J. Pharmacol. 370 (1999) 211-216.; J.H.M. Prehn, M. Welsch, C. Backhauss, J. Nuglisch, F. Ausmeier, C. Karkoutly, J. Krieglstein, Effects of serotonergic drugs in experimental brain ischemia: evidence for a protective role of serotonin in cerebral ischemia, Brain Res. 630 (1993) 110-120.; I. Semkova, P. Wolz, J. Krieglstein, Neuroprotective effect of 5-HT(1A) receptor agonist, Bay x 3702, demonstrated in vitro and in vivo, Eur. J. Pharmacol. 359 (1998) 251-260.; B. Suchanek, H. Struppeck, T. Fahrig, The 5-HT(1A) receptor agonist, Bay x 3702, prevents staurosporine-induced apoptosis, Eur. J. Pharmacol. 355 (1998) 95-101.] and to increase the release of the neurotrophic protein, S-100beta [P.M. Whitaker-Azmitia, R. Murphy, E.C. Azmitia, Stimulation of astroglial 5-HT(1A) receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology, Brain Res. 497 (1989) 80-86. ; P.M. Whitaker-Azmitia, R. Murphy, E.C. Azmitia, S-100 protein is released from astroglial cells by stimulation of 5-HT(1A) receptors, Brain Res. 528 (1990) 155-158.]. In this study, we tried to find out whether S-100beta can protect cultured neurons from glutamate- and staurosporine-induced damage and whether the neuroprotective activity of the highly selective 5-HT(1A) receptor agonist, Bay x 3702, is mediated by an induction of S-100beta. Extracellularly added S-100beta (1-10 ng/ml) reduced staurosporine-induced damage in pure neuronal cultures from chick embryo telencephalon as well as in mixed neuronal/glial cultures from neonatal rat hippocampus. In addition, S-100beta (1 ng/ml) reduced neuronal death induced by exposure to glutamate (0.25 mM, 30 min) in mixed neuronal/glial cultures from neonatal rat hippocampus. In cultured rat cortical astrocytes, a 24 h-treatment with Bay x 3702 (1 nM) increased the S-100beta content in the culture medium from 2.2+/-0.3 (controls) to 6.2+/-0.7 ng/ml. In the adult rat, a 4 h-infusion of 4 microg/kg Bay x 3702 (i.v.) was found to increase the S-100beta content in the striatum 6 h after the beginning of the infusion to 153+/-37 microg/g compared with 60+/-20 microg/g in vehicle-treated rats. Bay x 3702 had no effect on the S-100beta content in the rat hippocampus. Finally, we tried to block the protective effect of Bay x 3702 against staurosporine-induced damage in mixed neuronal/glial cultures from rat neonatal hippocampus by anti-S-100beta antibodies. We found only a partial blockade, although the antibodies fully blocked the antiapoptotic effect of S-100beta itself demonstrating that the antibody was effective in blocking neuroprotection by S-100beta. Thus, we conclude that S-100beta was able to protect cultured neurons against glutamate- and staurosporine-induced damage. Furthermore, S-100beta mediated partially the protective effect of the 5-HT(1A) receptor agonist, Bay x 3702, against staurosporine-induced apoptosis in mixed neuronal/glial cultures from neonatal rat hippocampus.
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PMID:S-100beta protects cultured neurons against glutamate- and staurosporine-induced damage and is involved in the antiapoptotic action of the 5 HT(1A)-receptor agonist, Bay x 3702. 1070 Jun 4

It has recently been shown that 5-HT(1A) receptor stimulation reduced the infarct volume after occlusion of the middle cerebral artery in rats. Since there is increasing evidence that apoptosis is involved in neurodegenerative diseases and stroke, we investigated whether the 5-HT(1A) agonist Bay x 3702 could protect neurons against apoptotic damage in a rat model of transient forebrain cerebral ischemia. Bay x 3702 (4 microg/kg i.v.) caused a 10% reduction of neuronal damage in the hippocampal CA1 subfield. Higher doses of Bay x 3702 (40 and 12 microg/kg i.v.) did not cause any neuroprotective effect, most likely because of the strong reduction of mean arterial blood pressure during the period of Bay x 3702 infusion. Bay x 3702 (4 microg/kg i.v.) diminished DNA laddering in the hippocampus and striatum 4 days after 10 min forebrain ischemia. These results were confirmed by TUNEL-staining. The anti-apoptotic effect was abolished by additional treatment with the 5-HT(1A) receptor antagonist WAY 100635 (1 mg/kg). Taken together, the results suggest that Bay x 3702 can rescue hippocampal as well as striatal neurons from apoptotic cell death in vivo via stimulation of 5-HT(1A) receptors.
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PMID:Stimulation of 5-HT(1A) receptors reduces apoptosis after transient forebrain ischemia in the rat. 1106 86


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