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

The present study was designed to examine the effect of blood glucose level on survival and pathologic changes of the cortical neuronal cells during and after three-hour incomplete cerebral ischemia, which was induced by bilateral carotid artery ligation in spontaneously hypertensive rats (SHRs). Blood glucose levels were varied by intraperitoneal infusion of 50% glucose (hyperglycemia) or insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). None of the hyperglycemic or normoglycemic animals died during three-hour ischemia, whereas 45% of hypoglycemic animals died (p greater than 0.001). The survival rate for twenty-four hours after recirculation was in the following ascending order: hypoglycemia, normoglycemia, and hyperglycemia. Neither hypoglycemia nor hyperglycemia (38-392 mg/dL) in nonischemic animals developed any morphologic changes in the cerebral cortex. However, both the ischemic and recirculated brains showed various degrees of histologic changes such as shrinkage of the neuronal cells with cytoplasmic vacuoles, perineuronal edema, and swelling of neuropils. Such ischemic damage of the brain was more marked in hypoglycemic animals than in hyperglycemic or normoglycemic ones during ischemia, as well as one hour after recirculation. The results suggest that cerebral ischemia and its outcome become more deleterious in hypoglycemic than in normoglycemic and hyperglycemic states. On the other hand, hyperglycemia is not necessarily a disadvantage in acute cerebral ischemia with or without reperfusion in this model.
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PMID:Effect of blood glucose level in acute cerebral ischemia in spontaneously hypertensive rats--survival and brain pathology. 186 14

Several studies indicate that spreading depression is fundamentally related to seizure marches and to the aura of classical migraine. Moreover, recent investigations call attention to its possible relevance in clinical disturbances associated with brain ischemia, trauma, and hypoglycemia. The anticonvulsant phenytoin has been shown to protect the nervous tissue from the effects of anoxia and ischemia. These properties suggest that phenytoin should be able to counteract spreading depression. Therefore, we investigated its effect on spreading depression elicited by mechanical or chemical (KCl) stimulation, in isolated chick retinas. The results showed that phenytoin: (1) increases the threshold concentration of KCl to initiate the phenomenon; (2) decreases the velocity of propagation of spreading depression; (3) shortens considerably the duration of the slow potential, ionic (K+, Ca2+, Cl-), and volume changes of the extracellular compartment during spreading depression. Possible mechanisms underlying the observed effects are discussed.
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PMID:Phenytoin and retinal spreading depression. 191 49

Insulin, an endogenously produced circulating peptide that enters the brain, has been shown to reduce ischemic brain and spinal cord damage in several animal models. Because of its potential clinical use in humans, the present study was undertaken to test the hypotheses that (a) survival and regional ischemic brain necrosis are improved by insulin; (b) insulin requires concomitant hypoglycemia to exert its neuroprotective effect; (c) insulin is still neuroprotective with delayed administration after an episode of postischemic hypotension; and (d) insulin is beneficial after normoglycemic, as well as hyperglycemic ischemia. Rats were subjected to 10.5 min two-vessel occlusion forebrain ischemia followed by 30 min of hypotension to increase the infarction rate. Insulin administered concomitantly with glucose significantly reduced the seizure rate, as well as cortical and striatal neuronal necrosis below that seen in untreated animals. Neuroprotection was seen whether insulin was given before or after a 30-min episode of postischemic hypotension. Insulin reduced pan-necrosis in addition to selective neuronal necrosis: The infarction rate was reduced in the cerebral cortex, thalamus, and substantia nigra pars reticulata. Normoglycemic ischemia produced only selective neuronal necrosis, but a beneficial effect on structural damage was also seen. The results indicate that insulin acts directly on the brain, independent of hypoglycemia, to reduce ischemic brain necrosis. Possible direct CNS mechanisms of action include an effect on central insulin receptors mediating inhibitory neuromodulation, an effect on central neurotransmitters, or a growth factor effect of insulin.
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PMID:Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. 193 78

Acute neurological injury from hypoxia-ischemia, hypoglycemia, and trauma is thought to be predominantly mediated by activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in the brain and the subsequent influx of calcium ions through receptor-operated channels. Several chronic degenerative diseases, such as Huntington's disease and the amyotrophic lateral sclerosis-Parkinsonism-dementia complex found on Guam, may share a similar pathogenesis due to a glutamate-like toxin. This laboratory recently reported that exposure to a reducing agent, such as dithiothreitol (DTT), selectively increases ionic current flow through NMDA-activated channels in several types of central neurons; conversely, oxidizing agents reverse this effect. To investigate the novel influence of redox modulation on NMDA neurotoxicity, in the present in vitro study we monitored survival of an identified central neuron, the retinal ganglion cell, approximately 24 h after a brief exposure to DTT. To determine the degree of killing specifically related to activation of the NMDA receptor, 2-amino-5-phosphonovalerate (APV, a selective NMDA antagonist) was added to sibling cultures. APV-preventable, glutamate-induced death was increased 70 +/- 9% with DTT treatment. This effect was totally blocked by the concomitant addition of an oxidizing agent, 5,5-dithiobis-2-nitrobenzoic acid (DTNB). These findings suggest that the enhanced killing following chemical reduction with DTT is mediated at the NMDA receptor site, and that the redox state of the NMDA receptor is crucial for the survival of neurons facing glutamate-related injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Redox modulation of NMDA receptor-mediated toxicity in mammalian central neurons. 197 Jan 45

Activation of N-methyl-D-aspartate (NMDA) receptors is thought to mediate toxic damage to central neurons due to hypoxia-ischemia, hypoglycemia, and trauma. We studied identified rat retinal ganglion cell neurons in vitro, a useful system for the study of excitotoxicity, and compared the protective effects of delayed administration of a competitive antagonist, 2-amino-5-phosphonovalerate (APV), and of an uncompetitive antagonist, MK-801, after glutamate-induced injury. We used maximally protective doses of the 2 antagonists. Under these conditions, both antagonists were able to prevent neuronal cell death if they were present within minutes of exposure to an endogenous glutamate-related toxin. In contrast, MK-801, but not APV, protected significantly against NMDA-mediated neurotoxicity when administered 1 to 4 hours after the initial insult. Thus, at least under certain conditions, an uncompetitive NMDA antagonist may offer a distinct advantage over a competitive antagonist when given several hours after a neurologic injury.
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PMID:Comparison of delayed administration of competitive and uncompetitive antagonists in preventing NMDA receptor-mediated neuronal death. 197 Apr 28

Amino acids such as L-glutamate und L-aspartate are major excitatory neurotransmitters in the mammalian central nervous system (CNS) and potential neurotoxins (excitotoxins), which can destroy central neurons by excessive activation of respective receptors. In the last three decades evidence has accumulated that excitatory amino acids (EAA) are involved in many neurological diseases and that pharmacological intervention offers prospects of novel and more effective therapies. Three different receptor types for EAA have been identified, each being named by the selective agonist to which it is preferentially sensitive, i.e. N-methyl-D-aspartate- (NMDA), kainate- and quisqualate-receptors. In this review interest is focused primarily on the NMDA-receptor, whose structure has been subject of numerous electrophysiological and biochemical studies. Today, it is well established that the NMDA-receptor-ionophore complex has an agonist binding site for glutamate, NMDA and related EAAs which is coupled with an ion channel permeable to Na+, K+, Cl- and Ca2+. Four other binding sites for glycine, phencyclidine, Mg2+ and Zn2+ have been identified which can differentially modulate the function of the NMDA receptor. An additional polyamine binding site has recently been reported. Numerous studies on experimental animals demonstrate that modulators of NMDA-mediated neurotransmission may have antiepileptic, anxiolytic, muscle-relaxant and memory-enhancing effects. Particular interest has gained the possible neuroprotective efficacy of NMDA-receptor antagonists in neurological diseases such as hypoxia/ischemia, hypoglycemia, epilepsy and chronic neurodegenerative disorders (Huntington's, Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, and AIDS encephalopathy).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The N-methyl-D-aspartate receptor complex. Various sites of regulation and clinical consequences]. 197 26

Sclerosis of the cornu Ammonis or Ammon's horn sclerosis (AHS) is an "often-described, yet hitherto enigmatic phenomena" as Spielmyer put it in 1927. It has been found in cases with ischemia, anoxia or hypoglycemia and in more than half of the epileptic brains examined at autopsy. Various theories about its pathogenesis have been propounded. Among them, the "Pathoklise" theory of the Vogts and the vascular theory of Spielmeyer and his associates were prevailing until recently. In 1953, two articles were published to contribute to the pathogenesis of ictal automatism (a type of complex partial or temporal lobe seizures). One is the incisural sclerosis theory by Penfield and his associates and the other is the Ammon's horn sclerosis theory by Sano and Malamud. The former authors described a diffuse sclerosis of the infero-mesial temporal structures without, however, specifically relating it to AHS. They considered it was the result of localized anoxia of that portion of the brain caused by incisural herniation occurring during parturition. Sano and Malamud maintained that AHS is a result of convulsions, a distinct scar adjacent to which epileptogenic foci may develop in the course of time to cause ictal automatism. The latter theory was corroborated by Sano, Falconer and others. Falconer expanded the theory to the assertion that not only ictal automatism but other types of intractable epilepsy may be due to "mesial temporal (Ammon's horn) sclerosis". The most recent development in the pathogenesis of AHS is the excitotoxicity theory. Namely, AHS is caused by excessive excitation of neurons, probably by putative excitatory neurotransmitters, especially, glutamate. For this theory, there is a significant body of evidence. The problem of AHS, an old research subject and a matter of long-lasting controversy, has now been updated and become one of the newest topics in the field of experimental neurobiology.
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PMID:Ammon's horn sclerosis: its pathogenesis and clinical significance. 198 30

The mature, healthy, non-starved mammalian brain uses glucose only as a source of energy in the form of ATP, which is necessary for several metabolic processes, such as the maintenance of cellular homeostasis via ion homeostasis, maintenance of the integrity of cellular compartments, and intracellular transportation processes for the formation of several neurotransmitters, neurotransmission itself and a few anabolic reactions. Glucose breakdown contributes to the formation of the neurotransmitters: acetylcholine, glutamate, aspartate, gamma-aminobutyrate, and glycine. Normal cerebral aging is associated with an incipient perturbation in both cerebral glucose and related metabolism, that determines an energy deficit and thus an imbalance in cell homeostasis after the 7th or 8th decade of human life, indicating a threshold phenomenon. This is evidenced by morphological/morphobiological abnormalities comprising neuronal loss and structural changes. These events are thought to cause a marked reduction in the biological plasticity of the brain, which may be severely involved after additional stress situations such as ischemia, hypoxia or hypoglycemia. The age-related increasing perturbation of neuronal homeostasis may represent a stress situation capable of inducing heat shock proteins effecting gene activity. Thus, several age-related metabolic abnormalities at the cellular level, starting with a deficient neuronal glucose and energy metabolism, can be regarded as risk factors for neuronal damage and death, and hence reduced mental capacity.
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PMID:Brain glucose and energy metabolism during normal aging. 198 30

Transient periods of global cerebral ischemia lead to selective neuronal damage in the striatum. We investigated the effects of unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine (DA) system on the density and distribution of neuronal necrosis in the rat striatum following ischemia induced by bilateral occlusion of the common carotid arteries combined with hypotension. After both 12 and 15 min of ischemia, which caused slight and extensive striatal damage, respectively, there was no difference in the density of neuronal necrosis in the striatum between DA-lesioned and sham-operated animals. We conclude that the DA system alone does not modulate injury following complete cerebral ischemia, but may contribute significantly to damage following conditions such as during hypoglycemia and incomplete cerebral ischemia.
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PMID:Neuronal damage in the striatum following forebrain ischemia: lack of effect of selective lesions of mesostriatal dopamine neurons. 207 36

We used neonatal piglets to determine the influence of plasma glucose concentration on cerebral energy metabolism during and immediately after partial ischemia. We assessed cerebral metabolism using in vivo phosphorus-31 magnetic resonance spectroscopy. Arterial plasma glucose concentration was increased in four piglets by systemic infusions of dextrose in water for comparison with infusions of saline in four controls or decreased in eight piglets by fasting for 24-48 hours for comparison with four fed piglets. Plasma glucose concentration showed a significant linear correlation with intracellular pH (r = -0.7, p less than 0.05). Piglets that developed hypoglycemia during partial ischemia had a smaller reduction in intracellular pH and a larger increase in inorganic phosphate content than piglets that were normoglycemic or hyperglycemic during ischemia. Similar differences persisted during the first 5 minutes of postischemic reperfusion. Subsequently, the cerebral concentrations of phosphorylated compounds returned to normal in all piglets. Our results demonstrate that 1) arterial plasma glucose concentration influences cerebral energy metabolism and intracellular pH during ischemia, 2) neonatal piglets can develop profound brain acidosis, and 3) brain acidosis during ischemia does not influence the restoration of cerebral phosphorylated compounds to control levels during the first 90 minutes after ischemia.
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PMID:Effect of plasma glucose concentration on cerebral metabolism during partial ischemia in neonatal piglets. 210 36


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