UMLS:C0917798 - FACTA Search

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

The effect of treatment with the potent, non-competitive NMDA receptor-channel antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d] cyclohepten-5,10-imine maleate (MK-801) on ischemia-induced brain damage was studied in a well-characterized model of focal neocortical infarction in spontaneously hypertensive rats. Anesthesia exposure was minimized to the surgical procedure and the infarcts were allowed to mature over a 24-h period. Pretreatment with 5 mg/kg i.p. MK-801 (n = 11 control, n = 12 treated animals) 30 min before induction of focal cerebral ischemia had no statistically significant influence on infarct volumes. However, pre- and post-treatment with MK-801 5 mg/kg i.p. 30 min before induction of ischemia and 2.5 mg/kg each at 8 and 16 h after onset of ischemia, reduced infarct volumes in two separate studies by 29% (investigator J.T., n = 5 control and n = 7 treated animals) and 20% (investigator U.D., n = 8 control and n = 8 treated animals), respectively. The combined reduction in infarct volume in MK-801-treated animals for both investigators was 23% (P = 0.016, ANOVA). The findings indicate a smaller neuroprotective effect of MK-801 in spontaneously hypertensive rats subjected to focal ischemia than in previous reports using normotensive animals.
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PMID:Pre- and post-treatment with MK-801 but not pretreatment alone reduces neocortical damage after focal cerebral ischemia in the rat. 214 95

Elevated cerebral lactate levels following cerebral ischemia have been associated with brain cell damage and death. We previously found that pre- or postischemia treatment with dichloroacetate (DCA), presumably by its activation of brain pyruvate dehydrogenase, effectively lowers cerebral lactate levels in rats subjected to 30 minutes of partial global ischemia (PGI) followed by 30 minutes of recirculation. The goal of the present study was to determine the effects of preischemia DCA treatment on cortical lactate levels during the ischemia period or during early recirculation. Rats (four in each group) received preischemia treatment with DCA and were then subjected to 0, 10, or 30 minutes of PGI or 30 minutes of PGI followed by 15 minutes of recirculation. Cortical lactate levels in pretreated animals were not significantly different from lactate levels of untreated rats at any time during PGI, but were significantly lower than levels in untreated rats at 15 minutes of recirculation (P less than .05, ANOVA). These results suggest that preischemia treatment with DCA does not limit the accumulation of cortical lactate during PGI but may promote its clearance during recirculation following PGI. If reperfusion events influence the degree of brain cell injury, DCA may enhance cell recovery by lower cortical lactate levels in the reperfusion period.
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PMID:Brain lactate during partial global ischemia and reperfusion: effect of pretreatment with dichloroacetate in a rat model. 359 91

Brain tissue lactate, pyruvate, and adenosine triphosphate (ATP) were measured 60 min after bilateral carotid ligation in spontaneously hypertensive rats, of which hematocrit (HCT) was varied by exchanging with isovolemic homologous red cells, plasma or whole blood. Supratentorial lactate of the ischemic brain was increased more in high HCT (greater than or equal to 50%) and less in low HCT (30-39%) compared with normal HCT (40-49%). In very low HCT (less than 30%), however, lactate was increased to further extent compared with any other group of HCT (ANOVA p less than 0.0001). Lactate/pyruvate (L/P) ratio of the ischemic brain showed similar changes, namely U-shaped correlation to HCT. In contrast, supratentorial ATP was decreased more markedly in very low HCT, followed by high and normal HCT, and minimally decreased in low HCT, demonstrating an inverse U-shaped relationship to HCT. Mean arterial pressure and arterial acid-base parameters in ischemic animals did not differ among HCT groups. There were no HCT-related changes of brain metabolites in non-ischemic control rats. These findings indicate that cerebral ischemia following carotid ligation is more severe in high HCT but less in low HCT, probably due to hemodynamic effects of HCT changes. When HCT is reduced to below 30%, however, insufficient oxygen supply to the brain or anemic hypoxia may superimpose on ischemia, resulting in more markedly impairment of brain metabolism. The role of HCT as a cause of cerebral ischemia and its severity is discussed.
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PMID:Effects of hematocrit on brain metabolism in experimentally induced cerebral ischemia in spontaneously hypertensive rats (SHR). 393 3

Glutamate (GLU) is a neurotransmitter. Massive release of GLU and glycine (GLY) into the brain's extracellular space may be triggered by ischemia, and may result in acute neuronal lysis or delayed neuronal death. The aim of this study was to evaluate the possible relationship between hyperventilation and the level of GLU and GLY during brain ischemia. Rabbits were anesthetized with halothane and oxygen. Group 1 was allowed to hyperventilate (PaCO2 25-35 mmHg). PaCO2 was maintained throughout the study. Group 2 was a normal control group that maintained normocapnia. Two global cerebral ischemic episodes were produced. Microdialysate was collected during the periischemic and reperfusion periods from the dorsal hippocampus. GLU and GLY concentrations were determined using high-performance liquid chromatography. In the control group, GLU and GLY were significantly elevated during each episode of ischemia; these levels returned to baseline within 10 minutes after reperfusion. In contrast, in the hyperventilation group GLU and GLY concentrations increased during ischemia, but they were not statistically significant. Two way ANOVA for the periischemic periods (t = 15,80; p = 0.06) revealed lower GLU values for the hyperventilated animals. A similar analysis for periischemic GLY concentrations revealed significantly lower values in the hyperventilated group (t = 10,15,75,80: p = 0.03) as compared to normal controls. We were able to demonstrate that hypocapnia during periischemic period lowered extracellular GLU and GLY concentrations. These results can explain a part of the protective action of hypocapnia during cerebral ischemia.
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PMID:Effect of hypocapnia on extracellular glutamate and glycine concentrations during the periischemic period in rabbit hippocampus. 748 47

We investigated the effects of selective glutamate (Glu) agonists on the release of monoamine neurotransmitters and their implication in the enhanced monoamine release in cerebral ischemia. In the striatum of anesthetized Sprague-Dawley rats, in vivo microdialysis was performed and the release of excitatory amino acids (Glu and aspartate (Asp)) and monoamines (dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT)) was measured by high-performance liquid chromatography with an electrochemical detector. (1) Forebrain ischemia by 4-vessel occlusion generated significant correlations between the Glu and Asp levels and the DA, NE and 5-HT levels (r = 0.922-0.967, P < 0.01, n = 6). (2) L-Glu and its selective agonists (N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and kainate (KA)) evoked a simultaneous release of striatal DA, NE and 5-HT in a dose-dependent manner (P < 0.01, ANOVA, n = 8). The maximal monoamine release evoked by the Glu agonists showed different magnitudes in the order of DA >> NE > 5-HT (118-, 16- and 9-fold from the baseline levels by 62.5 mM L-Glu, respectively). Each Glu agonist exerted a different magnitude of transmitter release and the order of agonist efficacy was different among NE, 5-HT and DA release: AMPA = KA > L-Glu = NMDA for DA release, AMPA > L-Glu = NMDA = KA for NE release, and L-Glu = NMDA = KA = AMPA for 5-HT release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Presynaptic glutamate receptors facilitate release of norepinephrine and 5-hydroxytryptamine as well as dopamine in the normal and ischemic striatum. 783 79

Transit-time ultrasound methods were used to measure blood flow in 37 patients undergoing carotid endarterectomy. Internal carotid flow before (ICFbef) and after (ICFaft) endarterectomy was measured with a 6 mm perivascular probe, and Javid shunt flow (SF) was measured with a clamp-on probe. For the entire group ICFbef averaged 117 +/- 67 ml/min and ICFaft was 173 +/- 67 ml/min. Shunt flow averaged 123 +/- 51 ml/min. The differences between ICFbef and ICFaft and between SF and ICFaft were significant (ANOVA, p < 0.01) but the difference between ICFbef and SF was not. The relationship between ICFbef and SF appeared to define two groups of patients. Those in whom SF was greater than ICFbef (SF > ICFbef) had more stenosis evident on preoperative arteriograms (64.7% +/- 14.55% maximum single diameter stenosis) and a greater average increase in ICF (151% +/- 159%) than those with SF < or = ICFbef (43.3% +/- 20.9% stenosis and 34% +/- 54% increase in ICF), suggesting that the relationship between SF and ICFbef defines groups with different hemodynamic responses. The similarity between SF and ICFbef indicates that Javid shunt flow offers adequate protection from cerebral ischemia. A practical benefit of the shunt clamp-on flow probe is the ability afforded to recognize shunt occlusions.
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PMID:Intraoperative measurement of Javid shunt flow with transit-time ultrasound. 786 96

Repetitive cerebral ischemia in gerbils produces delayed neuronal damage in the substantia nigra reticulata (SNr). This damage begins 4 to 5 days after the insult and is severe by day 7. The damage can be attenuated by GABA agonists. There is a prominent GABAergic striatal pathway to the SNr. Damage to this pathway leads to progressive loss of SNr neurons. This loss can be prevented by GABA agonists. We postulate that, ischemia-induced lack of GABAergic inhibitory input from the striatum to the SNr, may be responsible for this delayed neuronal damage. In the present experiment, we have measured striatal extracellular GABA concentrations with or without nipecotic acid, a GABA-reuptake inhibitor, in gerbils exposed to repetitive ischemia. GABA levels were measured on days 1, 3, 5, and 7 after the ischemic insult. Five control animals and a similar number of ischemic animals were monitored on each day. Extracellular fluid was collected using in vivo microdialysis and GABA levels were measured by electrochemical detection with HPLC. The extracellular striatal GABA levels were very low in the initial three specimens collected, both in the control and in the ischemic animals. However, addition of nipecotic acid resulted in an immediate increase of GABA in measurable range. In comparison to the controls, the increase in GABA on day 1 and 3 were significantly higher in animals with repetitive ischemia (two-way ANOVA with repeated measures). Subsequent measurements showed a gradual decrease in GABA levels when compared to controls. The increase in GABA with nipecotic acid was significantly lower on day 7 after the ischemic insults when compared to the controls. The increased GABA responsiveness immediately after the ischemic insults may reflect a protective effect against excitotoxicity. The subsequent decline in GABA levels after the insult may be secondary to progressive loss of striatal GABAergic neurons. This may contribute to the production of delayed neural damage in the SNr by a decrease in the inhibitory striatal input.
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PMID:Progressive decrease in extracellular GABA concentrations in the post-ischemic period in the striatum: a microdialysis study. 788 74

We describe a rat model for middle cerebral artery occlusion and discuss its usefulness for the study of structural consequences of various ischemic periods. We inserted 4/0 polyethylene sutures into the external carotid artery of 48 Wistar rats. The tips were rounded and coated with a thin layer of dental silicone. By inserting a section 18 mm long we assured that placement of the tip was between the origins of the middle and anterior cerebral arteries. The suture was withdrawn at predetermined times to allow complete reflux through the common carotid. The animals were sacrificed 24 hours after this procedure and tested for the presence of infarct by staining with 2,3,5 triphenyl-tetrazolium on 2 mm coronal cuts. We identified several differences regarding areas of infarction after the different occlusion periods, as shown by ANOVA and Newman-Keuls testing. Thus, occlusion for 15 minutes did not provoke infarction; occlusion of 30, 45 and 60 minutes produced selective infarction of the caudate nucleus and putamen; and finally, incomplete cortical infarction appeared after 90 minutes and was complete after 2 hours, at which time infarction was similar to that seen after 24 hours of occlusion. Intravascular occlusion is a reliable method for inducing focal cerebral ischemia, enabling us to confirm the existence of an infarction time threshold that is longer for the cortex than for the caudate nucleus and putamen.
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PMID:[Temporal threshold for middle cerebral artery infarction]. 875 37

Nitric oxide (NO) increases 3',5'-cyclic guanosine monophosphate (cGMP) in vascular smooth muscle and increases cerebral blood flow (CBF). In early stages of cerebral ischemia, NO plays a beneficial role in sustaining CBF. Subarachnoid hemorrhage (SAH), one of the main causes of ischemia, may impair vascular reactivity to NO. To test the hypothesis, 48 h after SAH was induced in rats, we examined the CBF response to the NO donor, SIN-1 (3-morpholinosydnonimine). We measured CBF by laser-Doppler flowmetry in association with: (1) intracarotid injection (for 30 min) of SIN-1 (1.5 mg/kg), 8-bromo-cGMP (7.5 mg/kg), papaverin (1.5 mg/kg) or vehicle; (2) cortical superfusion (for 90 min) of SIN-1 (10(-5) M) or vehicle through the cranial window. Hypotension produced by these vasodilators was controlled with phenylephrine. Vehicle alone did not change CBF throughout the measurement. Intracarotid infusion of SIN-1 (n = 6/group) increased CBF up to 128.6 +/- 3.9% and 111.9 +/- 2.9% in the control group and the SAH group, respectively. SAH significantly attenuated the response (P < 0.05, ANOVA). SAH did not affect the CBF increases elicited by intracarotid administration of cGMP or papaverin, or cortical superfusion of SIN-1. We conclude that during chronic vasospasm SAH disturbs the pathway between NO release and cGMP production in large cerebral arteries. The impairment accounts for the fragility of the brain in the face of ischemia following SAH.
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PMID:Subarachnoid hemorrhage impairs cerebral blood flow response to nitric oxide but not to cyclic GMP in large cerebral arteries. 920 Apr 92

Free radicals have gained wide acceptance as mediators of cerebral ischemic injury. It has previously been reported that a spin trap nitrone, alpha-phenyl-N-tert-butyl nitrone (PBN), can reduce infarct volumes in rats subjected to either permanent or transient focal cerebral ischemia. A recent study has demonstrated that NXY-059, a novel free radical trapping nitrone compound, has a neuroprotective effect against transient focal cerebral ischemia. This study was designed to determine the effect of NXY-059 in a rodent model of permanent focal cerebral ischemia. Male spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion (MCAO) by placement of a microaneurysm clip on the middle cerebral artery (MCA). Animals were divided into three groups: (1) physiological saline given as a 1 ml/kg i.v. bolus administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 0.5 ml/h of physiological saline for 24 h (n=10); (2) 30 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 30 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=9); (3) 60 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 60 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=12). Infarction was quantified after a survival period of 24 h. Differences in infarct volume were examined with one-way ANOVA following Dunnet's multiple comparison test. The percentage of cortical infarction in the saline control group was 22.6 +/- 6.8% (mean+/-S.D.) of contra-lateral hemisphere, and in the 30 mg/kg/h NXY-059-treated group was 17.4% +/- 6.8% (NS). Plasma concentration (microM/l) of NXY-059 in the 30 mg/kg/h group was 80.2 +/- 52.2 (n=9), while in the 60 mg/kg/h group plasma concentration (microM/l) of NXY-059 was 391.0 +/- 207.0 (n=10). Infarction in the 60 mg/kg/h NXY-059-treated group was significantly reduced (P=0.009) to 14.5 +/- 5%. Our preliminary data demonstrate that administration of NXY-059 (60 mg/kg/h for 24 h) ameliorates cortical infarction in rats subjected to permanent focal cerebral ischemia with 24 h survival.
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PMID:NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat. 1147 19

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