Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During epileptogenesis a series of molecular and cellular events occur, culminating in an increase in neuronal excitability, leading to seizure initiation. The entorhinal cortex has been implicated in the generation of epileptic seizures in both humans and animal models of temporal lobe epilepsy. This hyperexcitability is due, in part, to proexcitatory changes in ion channel activity. Sodium channels play an important role in controlling neuronal excitability, and alterations in their activity could facilitate seizure initiation. We sought to investigate whether medial entorhinal cortex (mEC) layer II neurons become hyperexcitable and display proexcitatory behavior of Na channels during epileptogenesis. Experiments were conducted 7 days after electrical induction of status epilepticus (SE), a time point during the latent period of epileptogenesis and before the onset of seizures. mEC layer II stellate neurons from post-SE animals were hyperexcitable, eliciting action potentials at higher frequencies compared with control neurons. Na channel currents recorded from post-SE neurons revealed increases in Na current amplitudes, particularly persistent and resurgent currents, as well as depolarized shifts in inactivation parameters. Immunocytochemical studies revealed increases in voltage-gated Na (Nav) 1.6 isoform levels. The toxin 4,9-anhydro-tetrodotoxin, which has greater selectivity for Nav1.6 over other Na channel isoforms, suppressed neuronal hyperexcitability, reduced macroscopic Na currents, persistent and resurgent Na current densities, and abolished depolarized shifts in inactivation parameters in post-SE neurons. These studies support a potential role for Nav1.6 in facilitating the hyperexcitability of mEC layer II neurons during epileptogenesis.
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PMID:Evidence for a role of Nav1.6 in facilitating increases in neuronal hyperexcitability during epileptogenesis. 2374 Oct 36

Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. Using combined methods of behavioral testing, immunofluorescence and electrophysiological recordings, we characterized the anticonvulsant effect of RIN in a pilocarpine-induced status epilepticus (SE) rat model of temporal lobe epilepsy (TLE) and investigated the underlying cellular mechanisms. In one set of experiments, rats received RIN treatment prior to pilocarpine injection. In a second set of experiments, rats received RIN treatment following the onset of stage 3 seizures. Pretreatment and posttreatment with RIN effectively reduced the seizure severity in the acute phase of TLE. Furthermore, RIN protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated spontaneous epileptiform discharge of mEC layer II neurons in SE-experienced rats. Whole-cell voltage-clamp recordings indicated that RIN inhibited neuronal hyperexcitability via inhibition of the persistent sodium current (INaP) and NMDA receptor current. Immunofluorescence experiments also demonstrated that RIN rectified the pilocarpine-induced upregulation of Nav1.6 and NR2B protein expression. In conclusion, our results identified RIN as an anticonvulsant agent that inhibited ictal discharge via INap and NMDA receptor current inhibition.
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PMID:Anticonvulsant effect of Rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy. 2767 Sep 3

Temporal lobe epilepsy (TLE) is one of the most refractory types of adult epilepsy, and treatment options remain unsatisfactory. Gastrodin (GAS), a phenolic glucoside used in Chinese herbal medicine and derived from Gastrodia elata Blume, has been shown to have remarkable anticonvulsant effects on various models of epilepsy in vivo. However, the mechanisms of GAS as an anticonvulsant drug remain to be established. By utilizing a combination of behavioral surveys, immunofluorescence and electrophysiological recordings, the present study characterized the anticonvulsant effect of GAS in a pilocarpine-induced status epilepticus (SE) rat model of TLE and explored the underlying cellular mechanisms. We found that GAS pretreatment effectively reduced the severity of SE in the acute phase of TLE. Moreover, GAS protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated the SE-induced bursting discharge of mEC layer II neurons from SE-experienced rats. Furthermore, the current study revealed that GAS prevented the pilocarpine-induced enhancement of Nav1.6 currents (persistent (INaP) and resurgent (INaR) currents), which were reported to play a critical role in the generation of bursting spikes. Consistent with this result, GAS treatment reversed the expression of Nav1.6 protein in SE-experienced EC neurons. These results suggest that the inhibition of Nav1.6 sodium currents may be the underlying mechanism of GAS's anticonvulsant properties.
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PMID:Gastrodin Reduces the Severity of Status Epilepticus in the Rat Pilocarpine Model of Temporal Lobe Epilepsy by Inhibiting Nav1.6 Sodium Currents. 2774 86

Voltage-gated sodium channels (VGSCs) play a vital role in controlling neuronal excitability. Nav1.6 is the most abundantly expressed VGSCs subtype in the adult central nervous system and has been found to contribute to facilitate the hyperexcitability of neurons after electrical induction of status epilepticus (SE). To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct animal models of temporal lobe epilepsy (TLE) including a post-SE model induced by kainic acid (KA) intrahippocampal injection and a kindling model evoked by pentylenetetrazole (PTZ). A prominent, seizure intensity-dependent increase of Nav1.6 expression in reactive astrocytes was observed in ipsilateral hippocampus of post-SE rats, reaching the peak at 21 days after SE, a time point during the latent stage of epileptogenesis. However, Nav1.6 with low expression level was selectively expressed in the hippocampal neurons rather than astrocytes in PTZ-kindled animals. This seizure-related increase of a VGSCs subtype in reactive astrocytes after SE may represent a new mechanism for signal communication between neuron and glia in the course of epileptogenesis, facilitating the neuronal hyperexcitability.
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PMID:Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis. 2790 10

SCN8A encodes Nav1.6, one of the main voltage-gated sodium channel subunits in the brain, and SCN8A mutations lead to epileptic encephalopathy. Particular mutations render the mutant channel more susceptible to inhibition by phenytoin. Yet, the potentially severe side effects of phenytoin maintenance therapy, especially cognitive impairment, are undesirable in these already cognitively impaired patients. We describe a 5-year-old patient with SCN8A encephalopathy in whom phenytoin proved successful as emergency treatment to prevent clustering of seizures and status epilepticus, thus hospital stays. The ketogenic diet, levetiracetam, zonisamide, topiramate, and phenytoin maintenance therapy resulted in adverse reactions not previously documented in SCN8A encephalopathy.
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PMID:Phenytoin as a last-resort treatment in SCN8A encephalopathy. 2958 63