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

The effects on high-voltage activated (HVA) calcium currents were examined in hippocampal CA1 cells and dentate gyrus (DG) granule neurons, 2 days (short-term; ST) and 2-3 months (long-term; LT) after electrically induced, limbic electrographic and behavioural seizures in rats. Whole-cell voltage-clamp recordings in dissociated CA1 neurons of LT rats showed a decrease in the sustained HVA calcium current amplitude and a faster inactivation of the current both in rats that had experienced a status epilepticus (post-SE rats) and those in which the stimulation did not lead to SE (non-SE rats). In CA1 neurons of LT-SE rats this resulted in a reduced Ca2+ entry through the HVA channels. Perforated-patch voltage-clamp recordings in dissociated DG granule neurons of LT-SE rats showed an increased sustained HVA current amplitude compared to controls and non-SE rats, leading to an increased Ca2+ entry via HVA calcium channels. Two days after SE, we observed an increased Ca2+ entry for a defined depolarization, although the change in HVA current amplitude and inactivation rate did not reach significance. We also observed a decrease in calbindin-D28k staining in DG post-SE neurons, but this change was not associated with a change in HVA current inactivation. The opposite changes in neuronal Ca2+ entry through HVA channels in CA1 vs. DG cells depended strongly on whether rats had experienced SE and later spontaneous seizure activity. These changes are likely to contribute to regionally different effects on local network excitability.
 ...
PMID:Differential and long-lasting alterations of high-voltage activated calcium currents in CA1 and dentate granule neurons after status epilepticus. 1227 46

It has been suggested that calcium binding proteins protect against Ca2+ overload, thus rendering neurons more resistant against excitotoxicity. The influence of kainic acid, which induces status epilepticus, on the expressions of calbindin D28k, parvalbumin and calretinin was examined in the rat striatum by immunohistochemistry and microdensitometry. At 1, 3 and 6 days after kainic acid-induced seizure, the number of calretinin-positive neurons in the striatum was significantly lower than in control rats. However, no significant difference was observed in the number of calbindin D28k- and parvalbumin-positive neurons in control and seizure rats. At 1, 3 and 6 days after seizure the optical densities of calretinin- and parvalbumin-positive neurons in the striatum were significantly lower than in control rats. Our finding concerning the selective loss of calretinin-positive neurons in seizure groups suggests that calcium binding proteins in the striatum have differential vulnerabilities to kainic acid-induced seizure.
 ...
PMID:Differential changes of calcium binding proteins in the rat striatum after kainic acid-induced seizure. 1241 87

One of the oldest questions in epilepsy is whether seizures are a cause or a result of brain damage. Animal data have provided us with insights into the relationship between seizures and subsequent brain damage. It is now recognized that seizures can be caused by brain injury and that, in certain conditions, can cause brain damage. Whether seizures result in brain damage depends on a number of variables, including age of the animal, seizure type and duration, etiology of the seizures, and genetic substrate on which the seizures occur. Seizures lasting for hours can cause injury to the brain regardless of whether they are generalized or focal in onset. The cell loss that occurs after the seizure is secondary to excessive excitability, with seizures causing massive depolarization of neurons leading to excessive glutamate release. This glutamate release results in increased intracellular calcium, causing a cascade of changes that ultimately result in cell death. Hypoxia and ischemia can exacerbate the injury. However, even in animals that are well ventilated and oxygenated, prolonged seizures can lead to cell loss and subsequent reorganization of synaptic networks. Although prolonged seizures at any age can result in cell loss, the immature brain fares much better than the mature brain with regard to cell loss after a prolonged seizure. Evidence that prolonged seizures result in neuronal loss is firmly established. It is less clear how detrimental recurrent seizures are. Although cell loss and synaptic reorganization have been reported in recurrent seizure models, such as kindling, it is generally modest compared to status epilepticus. When seizure-induced changes do occur, the pathologic patterns in the brain differ from those in status epilepticus.
 ...
PMID:Seizure-induced neuronal injury: animal data. 1242 25

Multiple types of insults, such as status epilepticus, hypoxia and trauma, may alter the central nervous system. Strategies to protect the brain against insults remain a very difficult and challenging problem. Damage to the central nervous system can be modulated via excessive excitatory and reduced inhibitory neurotransmission. In addition, increased sodium and calcium loading through impaired voltage-sensitive channels, as well as alterations in the acid-base balance can contribute to both excitotoxic and apoptotic cell death. Epilepsy treatment has always been related to neuroprotection, since it aims to reduce the duration or totally suppress seizures. Although the debate on the capacity of simple seizures to induce neuronal injury is still ongoing, no doubt persists on the disastrous effects of prolonged episodes of status. The next step would be to prevent epilepsy. Several animal models have been used to study the various aspects of the epileptogenic process. In humans, one of the most compelling examples of a series of epileptogenic events is temporal lobe epilepsy (TLE). Temporal lobe epilepsy is often attributed to prolonged febrile convulsions in childhood resulting in mesial temporal sclerosis. However, the relationship between TLE, seizures in childhood and hippocampal sclerosis may not be apparent as initially believed. Furthermore, it is well recognized that in a number of patients there is a delay from a specific insult to the onset of seizures. This "latent period" could be an opportunity for effective intervention, provided that the underlying mechanisms are understood and that appropriate means for a beneficial modification of the disease process become available. The present review discusses the various steps of temporal lobe epilepsy and provides illustrations of the various mechanisms implicated in neuronal death. Data from animal models is also presented and illustrated with video sequences. Finally, on the basis of what is known on mechanisms of action of available antiepileptic drugs, some suggestions are put forward. Basic science and research are guided by clinical queries and from ongoing dialogue. The present illustrated review deals with only a small part of the important amount of work related to epilepsy and neuroprotection. As such it is necessarily schematic or even simplistic. The review is designed to inform clinicians about the basic issues related to the subject, thus allowing them to follow the ongoing debate and participate with pertinent questions. (Published with video sequences).
 ...
PMID:Epilepsy and neuroprotection: an illustrated review. 1244 19

Generation of free radicals may have a key role in the nerve cell damage induced by prolonged or frequently recurring convulsions (status epilepticus). Mitochondrial function may also be altered due to production of free radicals during seizures. We therefore studied changes in field potentials (fp) together with measurements of extracellular, intracellular, and intramitochondrial calcium concentration ([Ca(2+)]e, [Ca(2+)]i, and [Ca(2+)]m, respectively), mitochondrial membrane potential (deltapsi), NAD(P)H auto-fluorescence, and dihydroethidium (HEt) fluorescence in hippocampal slice cultures by means of simultaneous electrophysiological and microfluorimetric measurements. As reported previously, each seizure-like event (SLE) resulted in mitochondrial depolarization associated with a delayed rise in oxidation of HEt to ethidum, presumably indicating ROS production. We show here that repeated SLEs led to a decline in intracellular and intramitochondrial Ca(2+) signals despite unaltered Ca(2+) influx. Also, mitochondrial depolarization and the NAD(P)H signal became smaller during recurring SLEs. By contrast, the ethidium fluorescence rises remained constant or even increased from SLE to SLE. After about 15 SLEs, activity changed to continuous afterdischarges with steady depolarization of mitochondrial membranes. Staining with a cell death marker, propidium iodide, indicated widespread cell damage after 2 h of recurring SLEs. The free radical scavenger, alpha-tocopherol, protected the slice cultures against this damage and also reduced the ongoing impairment of NAD(P)H production. These findings suggest involvement of reactive oxygen species (ROS) of mitochondrial origin in the epileptic cell damage and that free radical scavenging may prevent status epilepticus-induced cell loss.
 ...
PMID:Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. 1246 17

Calsenilin is a neuronal calcium binding protein that may function in calcium signaling and cell death. Kainic acid, an analog of the excitatory amino acid L-glutamate, produced excitotoxic cell death and induced the pathophysiology of status epilepticus. The expression of calsenilin was investigated in the mouse brain after kainic acid-induced seizure and seizure-induced hippocampal neuronal cell culture system using immunostaining analysis. Calsenilin was markedly decreased not only in the damaged cortex and CA3 region of hippocampus at 24 h after kainic acid-induced seizure but also in a cell-culture model of seizure-like activity. In addition, immunoreactivity of calsenilin in the hippocampus derived from human epilepsy patient was significantly decreased compared with normal brain. These results demonstrate that the reduced expression of calsenilin may functionally be associated with the pathophysiology of status epilepticus.
 ...
PMID:Reduced expression of calsenilin/DREAM/KChIP3 in the brains of kainic acid-induced seizure and epilepsy patients. 1264 52

Neuronal nitric oxide synthase (nNOS) is a constitutively expressed and calcium-dependent enzyme. Despite predominantly expressed in neurons, nNOS has been also found in astrocytes, although at lower expression levels. We have studied the regulation of nNOS expression in cultured rat astrocytes from cortex and spinal cord by Western blotting and immunocytochemistry. nNOS was not detectable in cultured astrocytes grown in serum-containing medium (SCM), but was highly expressed after serum deprivation. Accordingly, calcium-dependent NOS activity and both intracellular nitrite levels and nitrotyrosine immunoreactivity after glutamate stimulation were higher in serum-deprived astrocytes than in cells grown in SCM. Serum deprivation induced a modification of astrocytes morphology, from flat to stellate. nNOS up-regulation was also observed in reactive astrocytes of rat hippocampi after electrically induced status epilepticus, as demonstrated by double-labeling experiments. Thus, nNOS upregulation occurs in both in vitro stellate and in vivo reactive astrocytes, suggesting a possible involvement of glial nNOS in neurological diseases characterized by reactive gliosis.
 ...
PMID:Upregulation of neuronal nitric oxide synthase in in vitro stellate astrocytes and in vivo reactive astrocytes after electrically induced status epilepticus. 1267 51

The amygdala is a critical brain region for limbic seizure activity, but the mechanisms underlying its epileptic susceptibility are obscure. Several lines of evidence implicate GluR5 (GLU(K5)) kainate receptors, a type of ionotropic glutamate receptor, in the amygdala's vulnerability to seizures and epileptogenesis. GluR5 mRNA is abundant in temporal lobe structures including the amygdala. Brain slice recordings indicate that GluR5 kainate receptors mediate a portion of the synaptic excitation of neurons in the rat basolateral amygdala. Whole-cell voltage-clamp studies demonstrate that GluR5 kainate receptor-mediated synaptic currents are inwardly rectifying and are likely to be calcium permeable. Prolonged activation of basolateral amygdala GluR5 kainate receptors results in enduring synaptic facilitation through a calcium-dependent process. The selective GluR5 kainate receptor agonist ATPA induces spontaneous epileptiform bursting that is sensitive to the GluR5 kainate receptor antagonist LY293558. Intra-amygdala infusion of ATPA in the rat induces limbic status epilepticus; in some animals, recurrent spontaneous seizures occur for months after the ATPA treatment. Together, these observations indicate that GluR5 kainate receptors have a unique role in triggering epileptiform activity in the amygdala and could participate in long-term plasticity mechanisms that underlie some forms of epileptogenesis. Accordingly, GluR5 kainate receptors represent a potential target for antiepileptic and antiepileptogenic drug treatments. Most antiepileptic drugs do not act through effects on glutamate receptors. However, topiramate at low concentrations causes slow inhibition of GluR5 kainate receptor-mediated synaptic currents in the basolateral amygdala, indicating that it may protect against seizures, at least in part, through suppression of GluR5 kainate receptor responses.
 ...
PMID:GluR5 kainate receptors, seizures, and the amygdala. 1272 56

Ca2+ currents are thought to enhance glutamate excitotoxicity. To investigate whether reduced expression of the Ca2+ limiting GluR2(B) subunit enhances seizure-induced vulnerability to either CA1 or CA3 neurons, we delivered GluR2(B) oligodeoxynucleotides (AS-ODNs) to the dorsal hippocampus of adult rats before inducing kainate (KA) seizures. After knockdown, no changes in behavior, electrographic activity, or histology were observed. In contrast, GluR2(B) knockdown and KA-induced status epilepticus produced accelerated histological injury to the ipsilateral CA3a-b and hilar subregions. At 8 to 12 h, the CA3a was preferentially labeled by both silver and TUNEL methods. TUNEL staining revealed 2 types of nuclei. They were round with uniform label, features of necrosis, or had DNA clumping or speckled chromatin deposits within surrounding cytosol, features of apoptosis. At 16 to 24 h, many CA3a-c neurons were shrunken, eosinophilic, argyrophilic, or completely absent. Immunohistochemistry revealed marked decreases in GluR2(B) subunits throughout the hippocampus, NR1 immunoreactivity was also reduced but to a lesser extent. In contrast, GluR1 and NR2A/B immunohistochemistry was relatively uniform except in regions of cell loss or within close proximity to the CA1 infusion site. At 144 h, the CA3 was still preferentially injured although bilateral CA1 injury was also observed in some AS-ODN-, S-ODN-, and KA-only-treated animals. Glutamate receptor antibodies revealed generalized decreases in the CA3 with all probes tested at this delayed time. In contrast, GluR2(B) expression was increased within CA1 irregularly shaped, injured neurons. Therefore, hippocampal deprivation of GluR2(B) subunits is insufficient to induce cell death in mature animals but may accelerate the already known CA3/hilar lesion, possibly by triggering apoptosis within CA3 neurons. CA1 and DG survive the first week despite their loss of GluR2(B) subunits, suggesting that other intrinsic properties such as increased Na+ conductance and reduced ability of the GluR2(B) subunit to interact with certain cytoplasmic proteins may be responsible for the augmented cell death rather than changes in AMPA receptor-mediated Ca2+ permeability. Alternatively, changes in allosteric interactions that affect other receptor classes of high density at the mossy fiber synapse (e.g. KA receptors) may augment KA neurotoxicity. Latent GluR2(B) increases in CA1 injured neurons support a role for AMPA receptor subunit alterations in seizure-induced tolerance.
 ...
PMID:GluR2(B) knockdown accelerates CA3 injury after kainate seizures. 1290

The relationship between alcohol and seizures is complex and multifaceted. The prevalence of epilepsy in alcohol-dependent patients of western industrialised countries may be at least triple that in the general population, whereas the prevalence of alcoholism is only slightly higher in patients with epilepsy than in the general population. The seizure threshold is raised by alcohol drinking and declines on cessation of drinking. As a result, during withdrawal from alcohol, usually 6-48 hours after the cessation of drinking, seizures may occur. Alcohol acts on the brain through several mechanisms that influence seizure threshold. These include effects on calcium and chloride flux through the ion-gated glutamate NMDA and GABA receptors. During prolonged intoxication, the CNS adapts to the effects of alcohol, resulting in tolerance; however, these adaptive effects seem to be transient, disappearing after alcohol intake is stopped. Although the relationship of seizures to alcohol use is likely to be dose dependent and causal, the available clinical data do not suggest that alcohol use results in seizure genesis. However, a genetic predisposition to alcohol withdrawal seizures is possible. Other seizures in alcohol-dependent individuals may be due to concurrent metabolic, toxic, infectious, traumatic, neoplastic and cerebrovascular diseases and are frequently partial-onset seizures. Alcohol abuse is a major precipitant of status epilepticus (9-25% of cases), which may even be the first-ever seizure type. Prompt treatment of alcohol withdrawal seizures is recommended to prevent status epilepticus. During the detoxification process, primary and secondary preventative measures can be taken. A meta-analysis of controlled trials for the primary prevention of alcohol withdrawal seizures demonstrated a highly significant risk reduction for seizures with benzodiazepines and antiepileptic drugs and an increased risk with antipsychotics. A meta-analysis of randomised, placebo-controlled trials for the secondary prevention of seizures after alcohol withdrawal showed lorazepam to be effective, whereas phenytoin was ineffective. Because withdrawal seizures do not recur if the patient remains abstinent, long-term administration of antiepileptic drugs is unnecessary in abstinent patients. The first seizure not related to alcohol withdrawal should not result in permanent drug treatment in an alcohol-dependent patient, because of poor compliance and the high likelihood of remission. The treatment of alcohol dependence is more important and should be prioritised before the prevention of further seizures.
 ...
PMID:Seizures in alcohol-dependent patients: epidemiology, pathophysiology and management. 1459 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>