Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0494475 (tonic-clonic seizure)
 1,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Direct unilateral intrastriatal stereotaxic injections of the selective ionotropic-type quisqualate receptor agonist, AMPA, in postnatal day 7 rats produced tonic-clonic seizure activity. Quantitative analysis of the severity of brain injury was assessed by comparison of the disparities in the weights of injected and contralateral cerebral hemispheres 3 days after the excitotoxin injection. The amount of AMPA that produced half-maximal brain injury was 9.5 nmol as assessed by comparison of disparities in cerebral hemisphere weights. In contrast, quisqualate was 26 times less potent. The marked susceptibility of the developing rat brain to AMPA toxicity may provide a useful model to assess the neuroprotective effectiveness and selectivity of ionotropic quisqualate receptor antagonists.
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PMID:The selective ionotropic-type quisqualate receptor agonist AMPA is a potent neurotoxin in immature rat brain. 196 8

Rats neonatally treated with 0.02% propylthiouracil (PTU) through mother's milk showed a high incidence of audiogenic seizures after maturation. These audiogenic seizures were differently modified by MK-801 and NBQX; while intraperitoneal MK-801 equally inhibited running fit (RF) and generalized tonic-clonic seizure (GTCS), NBQX administered into cisterna ambiens significantly inhibited RF but not GTCS. The possible involvement of glutamate receptors in the inferior colliculus was further investigated using naive Sprague-Dawley rats injected with NMDA, AMPA or cyclothiazide, known as an inhibitor of desensitization of AMPA action. All drugs tested successfully induced RF followed by GTCS, resembling audiogenic seizures in PTU-treated rats. However, sound stimulation could augment AMPA-induced, but not NMDA-induced GTCS. Systemic administration with MK-801 potently blocked GTCS induced by AMPA/cyclothiazide, but the same drug failed to block RF after intracisternal injection with AMPA/cyclothiazide. Furthermore, intracisternal administration with NBQX significantly inhibited only RF induced by AMPA/cyclothiazide. The present study suggests that: 1) glutamate receptors in the brainstem, possible in the inferior colliculus, play a crucial role in audiogenic seizures, namely the initiation of RF and propagation into GTCS; and 2) the initiation mechanism is regulated by both NMDA and AMPA receptors, whereas propagation is mainly controlled by NMDA receptors.
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PMID:[Running fit and generalized tonic-clonic seizure are differently controlled by different subtype receptors in the brainstem]. 986 27

Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity. In an acute hippocampal slice 4-aminopyridine (4-AP) epilepsy model in vitro, NBP decreased the epileptiform activity and miniature excitatory postsynaptic current (mEPSC) amplitude; there was no change in the miniature inhibitory postsynaptic current (mIPSC) amplitude or frequency. This effect suggested changes in excitatory synaptic transmission, which was altered through postsynaptic GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs). These findings showed that NBP suppressed epileptiform activity in these epilepsy models and provided the first detailed electrophysiological analysis of the impact of NBP in epilepsy models, which may be employed in future experimental or clinical therapies for patients with epilepsy.
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PMID:Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models. 2922 86