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

This experiment evaluated the potential for ketamine HCl, a non-competitive glutamate antagonist, to minimize injury resulting from temporary focal cerebral ischemia. Male spontaneously hypertensive rats were randomly assigned to receive either ketamine (n = 13) or halothane anesthesia (n = 12) during 2 h of reversible middle cerebral artery occlusion (MCAO). Ketamine was administered as a 50 mg/kg i.v. loading dose followed by a continuous 1.25 mg/kg/min i.v. infusion beginning 25 min prior to ischemia and continued until 30 min after reperfusion. An additional group of rats (ketamine-shams, n = 8) underwent craniectomy and ketamine administration (as above) but the middle cerebral artery was not ligated. Physiologic values were similar between groups with the exception of plasma glucose which was elevated in the halothane-MCAO group. After 4 days recovery, rats in all groups were neurologically evaluated. There were no differences between the two groups undergoing MCAO for neurologic grading or open field behavior, although both groups performed worse than did ketamine-shams (P less than 0.05). In contrast, motor performance revealed more severe deficits in the ketamine-MCAO rats vs either the halothane-MCAO or ketamine-sham groups (P less than 0.05). Cerebral infarct volume was then planimetrically measured after triphenyl tetrazolium chloride (TTC) staining of fresh brain sections. Mean +/- S.D. infarct volume was not different between the halothane-MCAO (134 +/- 51 mm3) and ketamine-MCAO (131 +/- 64 mm3) groups. Seven of 8 sham rats were free of TTC demarcated injury and in the remaining rat injury was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ketamine on outcome from temporary middle cerebral artery occlusion in the spontaneously hypertensive rat. 177 49

Excitatory amino acids (EAAs) have been implicated to play a part in the development of hypoxic-ischemic brain injury in the neonate. The aim of the present study was to follow changes of intra- and extracellular (microdialysis) amino acids in the cerebral cortex in a model where cortical hypoxic-ischemic damage is produced consistently. Hypoxic-ischemia (unilateral ligation of the carotid artery + 2 h of exposure to 7.8% oxygen) caused a depletion of tissue ATP, phosphocreatine and glucose with a concomittant accumulation of AMP and lactic acid in cortical tissue. These changes were accompanied by a decrease of tissue aspartate and glutamine whereas the contents of gamma-aminobutyric acid (GABA), phenylalanine, leucine, isoleucine, valine and alanine increased. In the extracellular fluid GABA, glutamate, aspartate, taurine, glycine and alanine all increased multi-fold during hypoxic-ischemia. Aspartate and glutamate returned to near initial levels 2 h after the end of the insult, whereas the elevation of glycine persisted during recovery. In conclusion, the high extracellular levels of EAAs and glycine may exert injurious effects during and after hypoxic-ischemia.
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PMID:Intra- and extracellular changes of amino acids in the cerebral cortex of the neonatal rat during hypoxic-ischemia. 178 36

It has been reported that basic fibroblast growth factor (bFGF) can increase neuronal survival and neurite extension, and that it further antagonizes the excitotoxicity of glutamate in in vitro hippocampal neurons. We examined the effects of bFGF on neuronal damage after transient forebrain ischemia. Rats were subjected to 20 min of cerebral ischemia in a four vessel occlusion model. Thirty minutes before induction of ischemia, bFGF (0.3-300 nM) or bFGF (300 nM) with heparin was applied to the hippocampal CA1 subfield. Morphological changes in the CA1 subfield were evaluated 7 days after ischemia and compared with those in the vehicle-injected group. A single injection of bFGF did not prevent postischemic neuronal damage in the hippocampal CA1, but these results do not rule out an effect of bFGF on neuronal damage after ischemia.
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PMID:Failure of basic fibroblast growth factor to prevent postischemic neuronal damage in the rat. 179 62

Results of recent biochemical and electrophysiological studies have suggested that a recognition site for polyamines exists as part of the NMDA receptor complex. This site appears to be distinct from previously described binding sites for glutamate, glycine, Mg++,Zn++, and open-channel blockers such as MK-801. The endogenous polyamines spermine and spermidine increase the binding of open-channel blockers and increase NMDA-elicited currents in cultured neurons. These polyamines have been termed agonists at the polyamine recognition site. Studies of the effects of natural and synthetic polyamines on the binding of [3H]MK-801 and on NMDA-elicited currents in cultured neurons have led to the identification of compounds classified as partial agonists, antagonists, and inverse agonists at the polyamine recognition site. Polyamines have also been found to affect the binding of ligands to the recognition sites for glutamate and glycine. However, these effects may be mediated at a site distinct from that at which polyamines act to modulate the binding of open-channel blockers. Endogenous polyamines may modulate excitatory synaptic transmission by acting at the polyamine recognition site of the NMDA receptor. This site could represent a novel therapeutic target for the treatment of ischemia-induced neurotoxicity, epilepsy, and neurodegenerative diseases.
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PMID:Modulation of the NMDA receptor by polyamines. 182 28

The experiments were designed to test the possibility that calcium influx into neurons via voltage sensitive calcium channels (VSCCs) contribute to brain damage in two conditions in which any amelioration of neuronal necrosis may be assumed not to occur through an improvement of blood flow, viz., hypoglycemic coma and brief transient ischemia. Hypoglycemic coma is thought to lead to neuronal necrosis by release of glutamate and cellular influx of calcium during the insult, while damage due to brief transient ischemia may, at least in part, result from increased calcium cycling across cell membranes in the postinsult period. The insults were delivered to anesthetized rats, and the localization and density of neuronal necrosis were evaluated by histopathology following 1 week of recovery. One dihydropyridine calcium antagonist (isradipine), given in doses which have been reported to ameliorate ischemic damage due to stroke, failed to reduce damage incurred by 30 min of hypoglycemic coma, or 15 min of transient forebrain ischemia. Provided that it can be assumed that isradipine in the doses employed reduced calcium influx via VSCCs, the results support the notion that calcium influx through VSCCs plays only a minor pathogenetic role in global/forebrain ischemia or in hypoglycemia, and they suggest that the effect of blockers of VSCCs in stroke, if any, is due to both blockade of VSCCs and increase in blood flow.
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PMID:The effect of a dihydropyridine calcium antagonist (isradipine) on selective neuronal necrosis. 183 Aug 97

Antagonists for the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor may have therapeutic potential as neuroprotectant agents in conditions of neuronal degeneration that include brain ischemia, Huntington's chorea, and Alzheimer's disease. Here we have investigated the pharmacological actions of LY274614, a structurally novel competitive NMDA receptor antagonist, for pharmacological selectivity and neuroprotectant effects following systemic administration. LY274614 potently displaced NMDA receptor ([3H]CGS19755) binding (IC50 = 58.8 +/- 10.3 nM), but had no appreciable affinity at [3H]AMPA or [3H]kainate receptor sites at up to 10,000 nM. NMDA-induced convulsions in neonatal rats or NMDA-induced lethality in mice are potently and selectively antagonized by i.p. or p.o. LY274614. Oral doses showed a delayed but prolonged duration of effect. In adult rats, the neurodegenerative effects (loss of choline acetyltransferase activity) following the intrastriatal infusions of NMDA or quinolinate, but not kainate, were prevented by LY274614 (2.5 to 20 mg/kg i.p.). LY274614 is an effective neuroprotectant agent against NMDA receptor-induced toxicity when administered systemically and is a promising therapeutic agent for conditions where glutamate plays a role in the pathology of neuronal degeneration.
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PMID:Neuroprotectant effects of LY274614, a structurally novel systemically active competitive NMDA receptor antagonist. 183 88

Although neuronal death following brain ischemia was originally considered to be due to an energy deficiency resulting from an impaired respiratory chain, the observation of "delayed neuronal death" indicated some other factor. It is believed that delayed neuronal death after transient forebrain ischemia appears as a result of release of glutamate, an excitatory amino acid. In the present study, transient ischemia for 20 minutes in a rat four-vessel occlusion model was induced, and serial changes in histology and N-methyl-D-aspartate receptor (NMDA-R) binding were evaluated up to the chronic stage. Destruction of pyramidal cells and extensive astrocytic proliferation in the CA1 area of the hippocampus was completed by 10 days after cerebral ischemia followed by cerebral blood recirculation. However, the glutamate receptor subtype, NMDA-R, showed no change in all brain regions until after 10 days, but decreased in the hippocampus to 50% after 21 days despite no evidence of histological progression of neuronal death. The results show that the time course for appearance of light microscopic damage in the hippocampal region does not parallel that for depletion of NMDA-R binding sites.
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PMID:Loss of N-methyl-D-aspartate (NMDA) receptor binding in rat hippocampal areas at the chronic stage after transient forebrain ischemia: histological and NMDA receptor binding studies. 183 45

Ischemia may increase glutamate release, which can lead to neuronal damage. The therapeutic value of drugs that antagonize glutamate's effects are being investigated in CNS ischemia. This study examined the efficacy of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten- 5,10-imine hydrogen maleate], in reducing ischemic injury. We explored the limits of this therapy and different properties of MK-801 that might be involved in its neuroprotective actions. Two focal CNS ischemia models were used, a multiple cerebral embolic model (MCEM) and a rabbit spinal cord ischemia model (RSCIM). When animals were treated 5 minutes after the onset of injury, MK-801 was effective in reducing ischemic damage in both models. However, when treatment was delayed 10 minutes after the ischemic insult in the MCEM, no neuroprotection was observed even when the MK-801 dose was increased eightfold. We also did not find a beneficial effect of MK-801 pretreatment with a dose that was one tenth of the effective dose in the RSCIM. Studies using the (-) MK-801 isomer showed that MK-801 neuroprotection exhibited stereoselectivity. The contribution of anticonvulsant activity and sedation to MK-801's neuroprotective actions was examined indirectly using phenytoin and midazolam, respectively. Neither drug was effective in reducing ischemic injury in the MCEM. This suggests that MK-801's neuroprotective efficacy in ischemia is mediated through its NMDA receptor antagonist activity independent of its anticonvulsant or sedative properties. These results support the hypothesis that excessive NMDA receptor excitation may be involved in ischemic neuronal damage.
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PMID:Pharmacologic studies of the neuroprotective actions of a glutamate antagonist in ischemia. 183 96

The neuroprotective role of endogenous adenosine during forebrain ischemia elicited by 4-vessel occlusion in rats was assessed using the adenosine antagonist, theophylline (32 mg/kg). Despite an increase in the release of glutamate in the hippocampus during ischemia, theophylline did not alter the neurological and histological outcomes. These results indicate that endogenous adenosine does not act as an endogenous neuroprotector by modulating glutamate release in this model.
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PMID:Enhancement of endogenous excitatory amino acids by theophylline does not modify the behavioral and histological consequences of forebrain ischemia. 184 3

Barbiturates reduce cerebral activity which again reduce the cerebral metabolic rate probably by activating chloride channels and potentiating GABA's effects on these channels. Protection of the brain against hypoxia might theoretically occur by this mechanism, by vasoconstriction or by inhibiting calcium or glutamate. The barbiturates appear to have a positive effect in head-injury patients with high ICP uncontrollable by conventional therapy (in one study 5% of patients with a GCS < or = 7), and in animal studies of regional ischemia. No effect has been established in complete cerebral ischemia (cardiac arrest). The barbiturates have a depressant effect on the cardiovascular and respiratory systems, and the patients require intensive care. Thus there are some indications in the literature that the barbiturate treatment itself causes complications, and it is possible that this might cancel a potential beneficial effect in some patients. Clinically, the barbiturates are effective anticonvulsants, can be used in an attempt to control an elevated ICP uncontrollable by conventional means, and during transient ischemic episodes in the operating room with adequate monitoring and support systems already in place.
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PMID:Barbiturates in neuroanesthesia and neuro-intensive care. 184 34


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