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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuroprotective effects of felbamate were tested in a model of incomplete cerebral ischemia and hypoxia in 7-day-old rat pups. Felbamate pretreatment (300 mg/kg) reduced the surface of infarcted cortex following bilateral carotid ligation, by 42-49% compared to saline and dimethylsulfoxide (DMSO) controls, respectively. The number of necrotic neurons in the dentate gyrus was reduced by 77% over both DMSO controls and saline controls. These results suggest that felbamate deserves further evaluation for its therapeutic potential in hypoxia-ischemia.
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PMID:Felbamate reduces hypoxic-ischemic brain damage in vivo. 160 Oct 70

Felbamate, a novel dicarbamate anticonvulsant that blocks the glycine site of the N-methyl-D-aspartate receptor and protects the hippocampal slice from hypoxic damage, shows remarkably low toxicity in animals and in humans. Since most treatment of human cerebral ischemia will have to be delivered after the insult, we investigated the neuroprotective potency of post hoc felbamate in rat pups with bilateral carotid ligations exposed to an atmosphere of 6.5% O2 for 1 hour. Brain temperature was unaffected by surgery, hypoxia, or felbamate. Neuroprotection was greatest at 300 mg/kg, less effective at 200 and 400 mg/kg, and ineffective at 100 mg/kg. Post hoc felbamate (300 mg/kg) reduced the volume of infarction from 67% +/- 7% of neocortex in unmedicated rats to 32% +/- 8%, 51% +/- 12%, 38% +/- 19%, and 53% +/- 10% when given 0, 1, 2, and 4 hours after hypoxic exposure, respectively. By 6 hours, post hoc protection was no longer significant. Delayed neuronal necrosis in hippocampal granule cells was reduced from 156 +/- 33 neurons to 12 +/- 7 (0 hours, p < 0.01) and 37 +/- 17 (1 hour, p < 0.05). These effects were obtained at plasma concentrations (60 to 120 mg/ml) that have occasionally been reached without serious toxicity in human anticonvulsant trials. These data suggest that, in this animal model, felbamate given after a hypoxic-ischemic insult is effective in reducing cerebral infarction and extremely effective in preventing delayed neuronal necrosis, but that the window of opportunity for post hoc treatment is only 1 to 4 hours.
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PMID:Posthypoxic treatment with felbamate is neuroprotective in a rat model of hypoxia-ischemia. 823 47

Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a novel agent effective against maximal electroshock, pentylenetetrazol and other chemically induced seizures in mice and rats. Felbamate has been proposed as a novel anticonvulsant for the treatment of generalized tonic-clonic and complex partial seizures. In addition, felbamate has been shown to have neuroprotectant effects (in vitro and in vivo) in neonate models of cerebral ischemia. However, few existing studies have contributed to the elucidation of the mechanism of anticonvulsant and neuroprotectant action of felbamate. Because glycinergic mechanisms have been demonstrated to be involved with seizure disorders and neuroprotection, we investigated the binding interaction of felbamate with strychnine-insensitive glycine receptors and compared these findings with brain and plasma levels of felbamate after drug treatment. Inhibition of [3H]5,7-dichlorokynurenic acid (a high-affinity glycine receptor antagonist) binding by felbamate (IC50 = 374 microM) corresponded well with peak felbamate concentrations found in brain (683 and 759 microM) and plasma (679 and 807 microM) 8 hr after 300 (i.p.) or 500 mg/kg (p.o.) doses, respectively. Chemically diverse anticonvulsants tested and MK 801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine maleate] did not modulate [3H]5,7-dichlorokynurenic acid binding. Additional studies have shown that felbamate does not interact with other sites associated with the N-methyl-D-aspartate receptor complex. Thus, the data presented in this report strongly indicate a mechanism of action for felbamate through strychnine-insensitive glycine receptor interaction.
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PMID:Evidence for anticonvulsant and neuroprotectant action of felbamate mediated by strychnine-insensitive glycine receptors. 838 42

Felbamate is an antiepileptic drug whose action appears to occur mainly through an interaction with neurotransmission mediated by excitatory amino acids. We assessed its effectiveness in a model of transient global ischaemia in Mongolian gerbils. Dizocilpine (MK 801) was used for comparison. Treatment was given 10 min after transient forebrain ischaemia which was performed by occluding both common carotid arteries for 10 min. Felbamate (300 mg/kg i.p.) increased the number of surviving neurons in the CA1, CA2 and CA3 hippocampal cells. In particular, the CA1 area had a significantly higher number of surviving pyramidal neurons than that of vehicle-treated animals (67 +/- 11 vs 33 +/- 6 surviving neurons/mm; P < 0.05). No significant difference in density of surviving neurons was observed between dizocilpine (3 mg/kg i.p.) and vehicle (54 +/- 10 vs 33 +/- 6 surviving neurons/mm). The EEG results indicated that the effect of felbamate, used alone, is the same in the ischaemic-vehicle group as non-ischaemic group. Our results show that felbamate exerts neuroprotective effects in a model of severe cerebral ischaemia.
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PMID:Neuroprotective effects of felbamate on global ischaemia in Mongolian gerbils. 898 57

Somatosensory evoked potentials (SEPs) as well as change following transient cerebral ischemia in the gerbil were characterized in this study. SEPs were measured in each gerbil before ischemia (day -1), during ischemia, 10 min, 2, 4, 8, 24, 48 h and 8 days after recirculation. During bilateral carotid occlusion, SEP amplitude was dramatically reduced and central conduction time was significantly increased. During recirculation these values showed an improvement when compared to ischemic but not to control values. Moreover at 8 days of recirculation they were still statistically different from control values. Felbamate administration at the dose of 150 mg kg(-1), immediately after recirculation was shown to ameliorate neurophysiological recovery following cerebral ischemia.
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PMID:Changes in somatosensory evoked potentials following forebrain ischemia in the gerbils: effects of felbamate. 1022 54