Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate is the principal excitatory neurotransmitter in the brain and, as such, it inevitably plays a role in the initiation and spread of seizure activity. It also plays a critical role in epileptogenesis. The process of "kindling" limbic seizures in rodents by repeated electrical stimulation is dependent on activation of N-methyl-D-aspartate (NMDA) receptors. The function of these receptors is enhanced in the hippocampus of kindled rats and in the cerebral cortex of patients with focal epilepsy. Microdialysis studies show an increase in the extracellular concentration of glutamate and aspartate before or during seizure onset, suggesting that either enhanced amino acid release or impaired uptake contributes to seizure initiation. Glutamate antagonists selective for NMDA or non-NMDA receptors are potent anticonvulsants when given systemically in a wide variety of animal models of epilepsy. They are of limited efficacy against kindled seizures in rats and (on the basis of preliminary evidence) in patients with drug-refractory complex partial seizures. Cognitive side effects appear to be a significant problem with competitive, as well as noncompetitive, NMDA antagonists. Glutamate receptor antagonists provide significant protection against brain damage following global or focal cerebral ischemia or acute traumatic injury in rodent models. Anticonvulsant compounds of the lamotrigine type, which act on sodium channels and reduce ischemia-induced glutamate release, are cerebroprotective in rodent ischemia models and are free from the cognitive side effects of NMDA-receptor antagonists.
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PMID:The role of glutamate in epilepsy and other CNS disorders. 797 2

Stroke is one of the most important causes of acquired epilepsy in the adult population. While factors such as cortical involvement and haemorrhage have been associated with increased seizure risk, the mechanisms underlying the development of epilepsy after stroke remain unclear. One hypothesised mechanism is an excitotoxic effect of abnormal glutamate release following a stroke. Cerebral extracellular glutamate levels are known to rise in the setting of acute stroke, and numerous studies have implicated glutamate in the pathogenesis of seizures and epilepsy, both through direct measurement of glutamate from the epileptic brain and by analysis of receptors and transporters central to glutamate homeostasis. While experimental evidence suggests the cellular injury induced by glutamate exposure may lead to development of an epileptic phenotype, there is little direct data linking the rise in glutamate during stroke with the later development of epilepsy. Clinical research in this field has been hampered by the lack of non-invasive methods to measure cerebral glutamate. However, with the increasing availability of 7T MRI technology, Magnetic Resonance Spectroscopy is able to better resolve glutamate from other chemical species at this field strength, and Glutamate Chemical Exchange Saturation Transfer (GluCEST) imaging has been applied to localise epileptic foci in non-lesional focal epilepsy. This review outlines the evidence implicating a pivotal role for cerebral glutamate in the development of post-stroke epilepsy, and exploring the role of MRI in studying glutamate as a biomarker and therefore its suitability as a molecular target for anti-epileptogenic therapies. We hypothesise that the rise in glutamate levels in the setting of acute stroke is a clinically relevant biomarker for the development of post-stroke epilepsy.
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PMID:Role of cerebral glutamate in post-stroke epileptogenesis. 3179 40