Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary objective of this study was to attempt to induce excessive intraglial acidosis during ischemia by subjecting rats to an initial insult which leads to post insult accumulation of glycogen, presumed to accumulate primarily in astrocytes. The initial insults were 15 min of transient forebrain ischemia, 30 min of hypoglycemic coma, and intraperitonial injection of methionine-sulphoximine (MSO). In the first two of these insults, glycogen content in neocortex increased to 6-7 mM kg(-1) after 6 h of recovery, and in MSO-treated animals even higher values were measured 24 h after administration ( 12 mM kg(-1)). In spite of this glycogen loading, the amount of lactate formed during a subsequent ischemic insult (of 5-30 min duration) did not exceed values usually obtained during complete ischemia in animals with normal glycogen contents (tissue lactate contents of 15 mM kg(-1)) This was because appreciable amounts of glycogen (3-7 mM kg(-1)) remained undegraded even after 30 min of ischemia. The undigested part largely reflected the extra amount of glycogen accumulated after the initial insults. It is discussed whether this part is unavailable to degradation by phosphorylase.
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PMID:Glycogen accumulated in the brain following insults is not degraded during a subsequent period of ischemia. 912 Apr 90

Excitotoxicity has been proposed to contribute to neuronal loss in a broad spectrum of neurodegenerative conditions such as ischemia, hypoglycaemic coma or cerebral trauma. Excitotoxic neuronal injury appears to be mediated mainly by the over-activation of glutamate receptors, especially N-methyl-D-aspartate receptors, with subsequent excessive Ca2+ influx. Concurrent with the activation of glutamate-gated ion channels, metabotropic glutamate receptors (mGluR), which are G-protein coupled receptors, are also expected to be activated. Excessive stimulation of phospholipase C-coupled mGluR, mGluR1 and mGluRS, has been suggested to have neurotoxic consequences. However, the contribution of mGluR activation on excitotoxicity is still unclear and controversial. Here we report that, following ischemic and excitotoxic brain injuries, inactivation of mGluR1 does not prevent excitotoxic neuronal damage. Given the evidence that agonists at this group of mGluR promoted neuronal death in cerebrocortical cultures after oxygen-glucose deprivation or after N-methyl-D-aspartate exposure, our findings suggest that mGluR-mediated excitotoxicity is unlikely associated with mGluR1 but rather with other PLC-coupled mGluR.
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PMID:Evidence against a permissive role of the metabotropic glutamate receptor 1 in acute excitotoxicity. 917 62

Induction of the mitochondrial permeability transition (MPT) has been implicated in cellular apoptosis and in ischemia-reperfusion injury. During MPT, a channel in the inner mitochondrial membrane, the mitochondrial megachannel, opens and causes isolated mitochondria to swell. MPT and mitochondrial swelling is inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells. Treatment with CsA (50 mg/kg, i.v.) showed a robust reduction of brain damage when administered 30 min before insulin-induced hypoglycemic isoelectricity of 30 min duration. Ultrastructural examination of the dentate gyrus revealed a marked swelling of dendrites and mitochondria during the hypoglycemic insult. In CsA-treated animals, mitochondria resumed a normal and contracted appearance during and after the hypoglycemic insult. Treatment with FK 506 (2 mg/kg, i.v.), a compound with immunosuppressive action similar to that of CsA, was not protective. Studies on the swelling kinetics of isolated mitochondria from the hippocampus showed that CsA, but not FK 506, inhibits calcium ion-induced MPT. We conclude that CsA treatment during hypoglycemic coma inhibits the MPT and reduces damage and that mitochondria and the MPT are likely to be involved in the development of hypoglycemic brain damage in the rat.
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PMID:Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death. 965 Nov 98

Transient increases in extracellular K+ are observed under various conditions, including repetitive neuronal firing, anoxia, ischemia and hypoglycemic coma. We studied changes in cytoplasmic Ca2+ ([Ca2+]cyt) evoked by pulses of KCl in human neuroblastoma SH-SY5Y cells and rat dorsal root ganglia (DRG) neurons at 37 degrees C. A "pulse" of KCl evoked two transient increases in [Ca2+]cyt, one upon addition of KCl (K+on) and the other upon removal of KCl (K+off). The K+on transient has been described in many cell types and is initiated by the activation of voltage-dependent Ca2+ channels followed by Ca2+-evoked Ca2+ release from intracellular Ca2+ stores. The level of KCl necessary to evoke the K+off transient depends on the type of neuron, in SH-SY5Y cells it required 100 mM KCl, in most (but not all) of dorsal root ganglia neurons it could be detected with 100-200 mM KCl and in a very few dorsal root ganglia neurons it was detectable at 20-50 mM KCl. In SH-SY5Y cells, reduction of extracellular Ca2+ inhibited the K+on more strongly than the K+off and slowed the decay of K+off. Isoflurane (1 mM) reduced the K+on)- but not the K+off-peak. However, isoflurane slowed the decay of K+off. The nonspecific cationic channel blocker La3+ (100 microM) had an effect similar to that of isoflurane. Treatment with thapsigargin (TG) at a concentration known to only deplete IP3-sensitive Ca2+ stores did not affect K+on or K+off, suggesting that Ca2+ release from the IP3-sensitive Ca2+ stores does not contribute to K+on and K+off transients and that the thapsigargin-sensitive Ca2+ ATPases do not contribute significantly to the rise or decay rates of these transients. These findings indicate that a pulse of extracellular K+ produces two distinct transient increases in [Ca2+]cyt.
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PMID:Transient increases in extracellular K+ produce two pharmacological distinct cytosolic Ca2+ transients. 1564 42


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