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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concept of excitotoxicity, neuronal death produced by overstimulation of excitatory amino acid receptors, has become a popular way of explaining the pathogenesis of neuronal death in a variety of acute and chronic neurologic diseases. While there is strong evidence supporting the role of excitotoxicity in acute processes such as hypoxia/ischemia and hypoglycemia, the role of excitotoxicity in chronic neurologic disease is not firmly established. To account for the inter- and intraregional variations in pathology of different neurodegenerative disorders, we suggest two modified forms of the excitotoxic hypothesis in which specific populations of neurons become more vulnerable to excitotoxic insult either by (1) possessing abnormal excitatory amino acid receptor subtypes or (2) being afflicted by any disease process that impairs cellular energy metabolism or otherwise decreases neuronal membrane potential. In these ways, excitotoxicity may be a final common pathway of neuronal death in a variety of neurodegenerative diseases.
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PMID:Alternative excitotoxic hypotheses. 131 41

An in vitro model of ischemia was utilized to study the effects of both oxygen and glucose depletion on transmitter release from rat striatal slices. The spontaneous and stimulation-evoked releases of tritiated dopamine, gamma-aminobutyric acid, glutamate, and acetylcholine were measured. Hypoxia increased the evoked release of glutamate and dopamine without effect on the resting release. In contrast, hypoglycemia itself increased the resting release of dopamine. Hypoxia in combination with hypoglycemia provoked a massive release of glutamate, dopamine, and gamma-aminobutyric acid. The effect on acetylcholine release was less pronounced. Ca2+ withdrawal partly reduced the effect of hypoxia combined with hypoglycemia on dopamine release and application of tetrodotoxin (1 microM) abolished it. MK-801 (3 microM), an N-methyl-D-aspartate receptor antagonist, attenuated the effect of hypoxia and hypoglycemia on [3H]dopamine release. omega-Conotoxin (0.1 microM) had a similar effect on stimulation-evoked release under a hypoxic condition. The D2 receptor antagonist sulpiride (100 microM) failed to enhance the release of [3H]acetylcholine in hypoxia combined with hypoglycemia. It was suggested that in response to hypoxia combined with hypoglycemia there is a massive release of glutamate due to the increased firing rate which in turn releases dopamine from the axon terminals through stimulation of presynaptic N-methyl-D-aspartate receptors. Dopaminergic inhibitory control on ACh release seems not to be operative under conditions of hypoxia combined with hypoglycemia.
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PMID:Regulatory interactions among axon terminals affecting the release of different transmitters from rat striatal slices under hypoxic and hypoglycemic conditions. 135 92

Effect of WEB 1881 FU (nebracetam) on hypoxia and ischemia-induced impairment of 2-deoxyglucose (2DG) uptake and CA1 field potentials induced by hypoxia and hypoxia/hypoglycemia (ischemia) in rat brain slices was evaluated and compared to the findings obtained with pentobarbital and idebenone. Hippocampal and cortical slices were exposed to 15-20 min of ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced both 30 mM KCl-induced 2DG uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals in the hippocampus. Pretreatment of nebracetam at 1 mM or pentobarbital at 0.1 mM attenuated a decline of 2DG uptake and CA1 field potentials under the condition of ischemia. In addition, nebracetam and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampus under hypoxia for 45 min. Furthermore, these drugs also attenuated the decline of 2DG uptake induced by 10 mM glutamate for 20 min. However, treatment with idebenone did not recover the deficit of 2DG uptake and CA1 field potential. The present result suggests that nebracetam and pentobarbital exert neuroprotective actions against not only ischemia but also glutamate toxicity.
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PMID:Neuroprotective effect of WEB 1881 FU (nebracetam) on an ischemia-induced deficit of glucose uptake in rat hippocampal and cerebral cortical slices and CA1 field potential in hippocampal slices. 135 46

Effect of minaprine on hypoxia- or hypoxia/hypoglycemia (ischemia)-induced impairment of 2-deoxyglucose (2DG) uptake by rat hippocampal slices was evaluated. Since minaprine was found to possess both a stimulating effect on acetylcholine release and a blocking effect on 5-HT2 receptors, the improving effect of minaprine on impaired 2DG uptake was compared to the findings obtained with oxotremorine, ketanserin and pentobarbital. Hippocampal slices were exposed to 20-min ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced 30 mM KCl-induced 2DG uptake by the hippocampus. Pretreatment with minaprine, oxotremorine, pentobarbital and ketanserin attenuated the ischemia-induced decline of 2DG uptake. In addition, minaprine, oxotremorine and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampal slices under hypoxia for 45 min. The present results suggest that minaprine exerts a neuroprotective action against ischemia-induced deficit of energy metabolism in vitro.
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PMID:Protective effect of minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia. 136 Oct 12

The effect of 5-HT3 receptor agonists and antagonists on the hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 field potential elicited by stimulation of Schaffer collaterals was investigated using rat hippocampal slices. Treatment with the 5-HT3 receptor agonist, 2-methyl-5-HT (1-10 microM), exacerbated the ischemia-induced decreased in CA1 field potential, whereas treatment with the 5-HT3 receptor antagonist, Y-25130 (0.1-100 microM), or the 5-HT2 receptor antagonist, ketanserin (10, 100 microM), produced dose-dependent neuroprotection against the ischemia-induced decrease. However, in normal non-ischemic solution these treatments did not significantly change the CA1 field potential. The protective action of Y-25130 was blocked by co-treatment with 2-methyl-5-HT. The magnitude of protection in the Y-25130-treated group (EC50, 1.8 microM) was about 20 times greater than that in the ketanserin-treated group (EC50, 33 microM). The present study demonstrated that stimulation of 5-HT3 receptors plays a detrimental role in the development of ischemic damage, whereas blockade of the 5-HT3 receptor plays a neuroprotective role in ischemic damage, suggesting a facilitatory role of 5-HT neurons in ischemia-induced neuronal deficits.
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PMID:Neuroprotective effect of 5-HT3 receptor antagonist on ischemia-induced decrease in CA1 field potential in rat hippocampal slices. 145 43

To clarify the role of muscarinic acetylcholine receptors in the hypoxia/hypoglycemia (ischemia)-induced functional deficit in hippocampal neurons, we examined the effect of cholinergic drugs on ischemia-induced impairments of glucose uptake and CA1 field potentials in hippocampus slices. Muscarinic receptors were subdivided into M1 (high affinity for pirenzepine) and M2 (low affinity for pirenzepine) subtypes. The M1 receptor subtype is coupled to an increase in phosphoinositide hydrolysis and the M2 receptor subtype is associated with inhibition of adenylate cyclase. The greater potency of carbachol in stimulating phosphoinositide hydrolysis resulted in exacerbated ischemia-induced deficits. Treatment with the muscarinic receptor antagonists scopolamine and pirenzepine (M1 receptor-selective antagonist) had a strong dose-dependent protective effect against ischemia-induced deficits. Oxotremorine and McN-A-343, weak stimulators of phosphoinositide hydrolysis and strong inhibitors of adenylate cyclase, had a weak neuroprotective action against ischemia-induced deficits. These results suggest that stimulation of M1 muscarinic receptors coupled with an increase in phosphoinositide hydrolysis may play a facilitatory role in ischemia-induced deficits. Stimulation of M2 muscarinic receptors may play an inhibitory role in ischemia-induced neuronal deficits.
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PMID:Effect of muscarinic cholinergic drugs on ischemia-induced decreases in glucose uptake and CA1 field potentials in rat hippocampus slices. 145 86

The effects of adenosine (A) receptor agonists on ischemia-induced impairment of 2-deoxyglucose (2-DG) uptake by rat hippocampal slices was evaluated. Hippocampal slices were exposed to 20-min hypoxia + hypoglycemia (ischemia) and then returned to oxygenated and glucose-containing Krebs-Ringer solution for 6 h. Ischemia reduced 2-DG uptake in the hippocampal slices. The ischemia-induced reduction in 2-DG uptake was attenuated by pretreatment with A1 receptor agonists but not with A2 receptor agonists. 8-Phenyltheophylline, an A1 receptor antagonist, exacerbated the ischemia-induced decrease. The A1 receptor agonist-induced neuroprotective effect was blocked by co-treatment with 8-phenyltheophylline. The present study suggests that the A1 receptor-mediated function has a protective role in ischemia-induced decreases in glucose metabolism in hippocampal slices.
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PMID:A neuroprotective effect of adenosine A1-receptor agonists on ischemia-induced decrease in 2-deoxyglucose uptake in rat hippocampal slices. 146 71

Preischemic hyperglycemia, which raises tissue lactate content during ischemia, is known to aggravate ischemic brain damage. To explore the possibility that the enhanced lactic acidosis gives rise to osmotic damage, we studied the influence of a varied preischemic plasma glucose concentration on the early postischemic edema. Brain edema was measured by the specific-gravity technique. Brain and plasma osmolality were measured with a vapor pressure osmometer. We examined different brain regions in hyperglycemic and moderately hypoglycemic rats subjected to 15 min of forebrain ischemia, followed by recirculation for 5, 15, and 30 min. The decrease in specific gravity was compared with the increase in osmolality, to study whether the edema formation in the different groups correlated to the increase in tissue osmolality. We found edema formation to be most pronounced in frontoparietal cortex. In this structure and in hippocampus, statistically significant decreases of specific gravity were seen at all recirculation times studied. In caudoputamen, significant edema was seen only in the groups with 5 and 15 min of recirculation. Contrary to expectations, no difference was found between hyperglycemic and hyperglycemic animals. Tissue osmolality increased during ischemia in both the low and high glucose groups, but to a higher level in the latter (hypoglycemia 311 +/- 1 mmol kg-1, hyperglycemia 328 +/- 10 mmol kg-1; mean +/- SD, p less than 0.05). In the hyperglycemic group, brain osmolality remained elevated for the first 15 min of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of preischemic hyperglycemia on osmolality and early postischemic edema in the rat brain. 150 45

Experiments in adult animals have indicated that hyperglycemia accentuates whereas hypoglycemia ameliorates hypoxic-ischemic brain damage. To determine whether hypoglycemia is protective or deleterious to the perinatal brain subjected to hypoxia-ischemia, 7-d postnatal rats were rendered hypoglycemic either by receiving an s.c. injection of insulin or fasting for 12 h. All rat pups underwent unilateral common carotid artery ligation followed by exposure to 8% oxygen-balance nitrogen at 37 degrees C for 2 h. Control animals (no insulin or fasting) received s.c. injections of normal saline. Mean blood glucose concentrations were 5.4 +/- 0.1, 4.3 +/- 0.2, and 3.4 +/- 0.1 mmol/L for control, insulin, and fasted animals, respectively. Blood beta-hydroxybutyrate concentrations were identical (0.5 +/- 0.1 mmol/L) for control and insulin-treated animals, but more than doubled in concentration in the fasted animals (p less than 0.001). Mortality rates during hypoxia-ischemia were higher in the insulin-treated animals (30%) than in either the fasted (4%) or control (0%) animals (p less than 0.05). Fasted animals showed a significant reduction in hypoxic-ischemic brain damage as compared with either the insulin-treated or control animals. Insulin-treated animals were not significantly different from controls. The findings indicate that 1) insulin induced hypoglycemia does not provide a protective effect on perinatal hypoxic-ischemic brain damage, as in adults; and 2) fasting adequate to produce hypoglycemia and ketonemia improved neuropathologic outcome.
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PMID:Effect of insulin-induced and fasting hypoglycemia on perinatal hypoxic-ischemic brain damage. 154 41

Peripheral A-delta and C fibers are activated during the production of ischemic or tourniquet pain; however, individual metabolic or molecular factors responsible for neural activation are not known. To elucidate these mechanisms the in vitro corneal nerve preparation was used. Electrophysiologic effects of individual metabolic perturbations associated with ischemia (hypoxia, hypoglycemia, lactic acid, and decreased pH) were investigated on A-delta and C fiber nociceptors. Increased tonic action potential activity occurred in C fibers but not in A-delta fibers after ischemia. The conduction velocity of C fibers was 0.85 +/- 0.2 m/s (mean +/- SD). Under control conditions (n = 43) there was very little fluctuation in the baseline action potential frequency (+/- 3.2%). Hypoxia (n = 12) resulted in a 213 +/- 3.4% (mean +/- SD) increase in C fiber action potential frequency relative to control (P less than 0.001, ANOVA). L-glucose substitution for D-glucose (n = 8) increased C fiber discharge frequency by 653 +/- 28% relative to control (P less than 0.001) as did the combination of hypoxia and L-glucose substitution (n = 6) by 671 +/- 14%. Comparison of hypoxia versus hypoxia and hypoglycemia conditions did not show them to be statistically different (P greater than 0.5). Lactate (10-1000 micrograms/ml) at a pH of 6.9 or 7.4 did not alter the action potential discharge frequency in corneal C fibers (n = 5, P greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of C fibers by metabolic perturbations associated with tourniquet ischemia. 155 Feb 87


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