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)

Excessive activation of excitatory amino acid receptors has been implicated in the neuronal degeneration caused by ischemia, hypoglycemia, and prolonged seizures. We have observed directly the time course and regional vulnerability of hippocampal neurons to glutamate receptor-mediated injury in organotypic hippocampal cultures, a preparation which combines accessibility and long-term survival with preservation of regional differentiation and neuroanatomic organization. Cultures were incubated with the fluorescent dye propidium iodide which selectively enters and stains cells only after membrane damage. After 5 to 10 min of a 30-min exposure to kainate (100 microM), large neurons in the hilus of the dentate were first to become brightly fluorescent. Propidium staining subsequently appeared in the other regions of the hippocampus and increased to a maximum over the first 6 h of recovery. NMDA (10 microM) caused propidium staining that was limited to CA1 and the dentate gyrus of the cultures, sparing CA3, consistent with the regions of highest NMDA receptor density in vivo. Glutamate (1 mM) caused a delayed, progressive pattern of staining that began in CA1 (2 to 4 h after exposure), then extended to include CA3 and finally the dentate gyrus over the next 24 h. Release of LDH activity into the media was slower and less sensitive than propidium staining. Histologic degeneration was limited to neurons 24 h after agonist exposure and was consistent with the propidium staining. NMDA, kainate, and glutamate each produced a unique pattern of neuronal injury. Most notably, glutamate had low potency as a toxin and its pattern of neuronal injury was not reproduced by NMDA.
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PMID:Direct observation of the agonist-specific regional vulnerability to glutamate, NMDA, and kainate neurotoxicity in organotypic hippocampal cultures. 171 7

Nitric oxide-releasing drugs have been shown to reduce ischemia/reperfusion (I/R) injury by acting as radical scavengers. However, their therapeutic application is hampered by specific side effects and rapid bioreduction in vivo. The half-life and antioxidant activity of nitroxides may be enhanced by their covalent binding to human serum albumin, resulting in polynitroxyl albumin (PNA). Thus, PNA may represent a novel antioxidative drug. The objectives of this study were to elucidate 1) whether PNA is able to diminish I/R injury; 2) the most effective dose of PNA in vivo; and 3) whether the addition of the nitroxide tempol enhances and/or prolongs the effect of PNA. Experiments were performed using a 4-h tourniquet-induced ischemia model in the hamster dorsal skinfold chamber. In the first part, five groups (n = 6) of animals received an infusion of 1) 1% body weight (b.w.) saline (0.9%); 2) 0.5% b.w. albumin (20%); 3) 0.5% b.w. PNA (20%); 4) 1% b.w. albumin (20%); and 5) 1% b.w. PNA (20%) 15 min prior to reperfusion. In the second part of the study, tempol (17 mg/mL) was added either to albumin or PNA (1:9), and 0.5% b.w. of this solution was infused (Group 6: tempol + albumin 0.5% b.w.; Group 7: tempol + PNA 0.5% b.w.). Intravital fluorescence microscopy allowed for quantification of functional capillary density (FCD), leukocyte adherence, extravasation of fluorescein isothiocyanate-labeled Dextran and non-viable (Propidium-positive) cell count prior to ischemia and 0.5 h, 2 h, and 24 h after reperfusion. PNA and--to a lesser extent albumin--effectively reduced postischemic microvascular perfusion failure, leukocyte adhesion, and tissue injury. PNA was most effective in the dose 1% b.w. Although free oxygen radical scavenging seems to be an underlying mechanism leading to the beneficial effects of PNA on I/R injury, hemodilution and known radical scavenging properties of pure albumin contribute in part to the observed effects. Although the combination of tempol and PNA revealed further short-term effects on microvascular perfusion and leukocyte adhesion, it did not result in a long-term improvement of tissue injury.
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PMID:Impact of polynitroxylated albumin (PNA) and tempol on ischemia/reperfusion injury: intravital microscopic study in the dorsal skinfold chamber of the Syrian golden hamster. 1094 61

Necrosis was considered to be the solo mechanism for ischemia/reperfusion (I/R)-induced cell death. Recent evidence from I/R models of the heart, liver, kidney, and brain indicates that apoptosis is a major contributor to I/R-induced cell death. However, evidence of I/R-induced apoptosis in skeletal muscle is sparse and divided. The purpose for the present study was to investigate I/R-induced necrosis and apoptosis in the cells isolated from rat skeletal muscle. A rat gracilis muscle model was used. After surgical preparation, clamps were applied on the vascular pedicle to create 4 h of ischemia and released for 24 h of reperfusion (I/R, n = 10). Clamping was omitted in sham I/R rats (sham I/R, n = 10). The muscle samples were harvested after 24 h of reperfusion for the process of cell isolation. Cells were stained by Propidium Iodide (PI) or Annexin V-FITC or both. Twenty thousand cells from each muscle sample were scanned and analyzed by flow cytometry. The average percentage of live cells was 45 +/- 2% in the I/R group versus 65 +/- 3% in the sham I/R group (p < 0.01). The average percentage of necrotic cells was 18 +/- 1% in I/R versus 12 +/- 1% in sham I/R (p < 0.01). The average percentage of apoptotic cells was 40 +/- 3% in I/R versus 27 +/- 3% in sham I/R (p < 0.01). Our results clearly demonstrated that I/R not only causes necrosis, but also accelerates apoptosis in the cells isolated from rat skeletal muscle.
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PMID:Ischemia/reperfusion-induced necrosis and apoptosis in the cells isolated from rat skeletal muscle. 1790 74

Neuronal activity in vitro exhibits network bursts characterized by brief periods of increased spike rates. Recent work shows that a subpopulation of neurons reliably predicts the occurrence of network bursts. Here, we examined the role of burst predictors in cultures undergoing an in vitro model of cerebral ischemia. Dissociated primary cortical neurons were plated on multielectrode arrays and spontaneous activity was recorded at 17 days in vitro (DIV). This activity was characterized by neuronal avalanches where burst statistics followed a power law. We identified burst predictors as channels that consistently fired immediately prior to network bursts. The timing of these predictors relative to bursts followed a skewed distribution that differed sharply from a null model based on branching ratio. A portion of cultures were subjected to an excitotoxic insult (DIV 18). Propidium iodine and fluorescence imaging confirmed cell death in these cultures. While the insult did not alter the distribution of avalanches, it resulted in alterations in overall spike rates. Burst predictors, however, maintained baseline levels of activity. The resilience of burst predictors following excitotoxic insult suggests a key role of these units in maintaining network activity following injury, with implications for the selective effects of ischemia in the brain.
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PMID:Burst predicting neurons survive an in vitro glutamate injury model of cerebral ischemia. 2664 12