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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy--and inhibits progression to status epilepticus (SE). Seizures after traumatic brain injury (TBI) may contribute to pathophysiology. Thus, we hypothesized that endogenous adenosine, acting via A1 receptors, mediates antiepileptic benefit after experimental TBI. We subjected A1-receptor knockout (ko) mice, heterozygotes, and wild-type (wt) littermates (n=115) to controlled cortical impact (CCI). We used four outcome protocols in male mice: (1) observation for seizures, SE, and mortality in the initial 2 h, (2) assessment of seizure score (electroencephalogram (EEG)) in the initial 2 h, (3) assessment of mortality at 24 h across injury levels, and (4) serial assessment of arterial blood pressure, heart rate, blood gases, and hematocrit. Lastly, to assess the influence of gender on this observation, we observed female mice for seizures, SE, and mortality in the initial 2 h. Seizure activity was noted in 83% of male ko mice in the initial 2 h, but was seen in no heterozygotes and only 33% of wt (P<0.05). Seizures in wt were brief (1 to 2 secs). In contrast, SE involving lethal sustained (>1 h) tonic clonic activity was uniquely seen in ko mice after CCI (50% incidence in males), (P<0.05). Seizure score was twofold higher in ko mice after CCI versus either heterozygote or wt (P<0.05). An injury-intensity dose-response for 24 h mortality was seen in ko mice (P<0.05). Physiologic parameters were similar between genotypes. Seizures were seen in 100% of female ko mice after CCI versus 14% of heterozygotes and 25% wt (P<0.05) and SE was restricted to the ko mice (83% incidence). Our data suggest a critical endogenous anticonvulsant action of adenosine at A1 receptors early after experimental TBI.
J Cereb Blood Flow Metab 2006 Apr
PMID:Adenosine A1 receptor knockout mice develop lethal status epilepticus after experimental traumatic brain injury. 1612 Nov 25

Several studies have highlighted a delayed secondary pathology developing after reperfusion in animals subjected to prolonged cerebral ischemia, and recently we have shown that peri-infarct depolarizations (PIDs) occur not only during ischemia, but also in this delayed period of infarct maturation. Here we study the electrocorticographic (ECoG) manifestations of PIDs as signatures of developing secondary pathology. DC- and traditional AC-ECoG signals were recorded continuously from epidural, nonpolarizable electrodes during 2 h of middle cerebral artery occlusion (MCAo) and 22 h of reperfusion in freely behaving rats. During MCAo, seizures and PIDs recurred frequently and their incidence was significantly correlated. After reperfusion, seizures and PIDs ceased, and for the next several hours delta wave abnormalities dominated the ECoG with progressively increasing amplitude. After a variable period (5 to 15 h), the ECoG amplitude decremented with the onset of a prolonged repetitive series of PIDs. Initial PIDs in this delayed phase produced transient depressions of the high amplitude ECoG signal, but thereafter the ECoG was persistently attenuated, with no transient depressions during subsequent PIDs. The time of onset of postreperfusion PIDs, and hence measures of ECoG attenuation, correlated with 24 h infarct volumes. PIDs could always be detected in baseline shifts of the AC-ECoG signal with a low high-pass cutoff setting. These results suggest that delayed PIDs after reperfusion contribute to a complex secondary pathology involving delayed edema, intracranial hypertension, and hypoperfusion. The manifestation of PIDs in ECoG/electroencephalography recordings may enable continuous real-time monitoring of infarct progression.
J Cereb Blood Flow Metab 2006 May
PMID:AC electrocorticographic correlates of peri-infarct depolarizations during transient focal ischemia and reperfusion. 1617 10

The aim of this paper is to explain critical features of the human primary generalized epilepsies by investigating the dynamical bifurcations of a nonlinear model of the brain's mean field dynamics. The model treats the cortex as a medium for the propagation of waves of electrical activity, incorporating key physiological processes such as propagation delays, membrane physiology, and corticothalamic feedback. Previous analyses have demonstrated its descriptive validity in a wide range of healthy states and yielded specific predictions with regards to seizure phenomena. We show that mapping the structure of the nonlinear bifurcation set predicts a number of crucial dynamic processes, including the onset of periodic and chaotic dynamics as well as multistability. Quantitative study of electrophysiological data supports the validity of these predictions. Hence, we argue that the core electrophysiological and cognitive differences between tonic-clonic and absence seizures are predicted and interrelated by the global bifurcation diagram of the model's dynamics. The present study is the first to present a unifying explanation of these generalized seizures using the bifurcation analysis of a dynamical model of the brain.
Cereb Cortex 2006 Sep
PMID:A unifying explanation of primary generalized seizures through nonlinear brain modeling and bifurcation analysis. 1628 Apr 62

Epilepsy is a common neurologic disorder that manifests in diverse ways. There are numerous seizure types and numerous mechanisms by which the brain generates seizures. The two hallmarks of seizure generation are hyperexcitability of neurons and hypersynchrony of neural circuits. A large variety of mechanisms alters the balance between excitation and inhibition to predispose a local or widespread region of the brain to hyperexcitability and hypersynchrony. This review discusses five clinical syndromes that have seizures as a prominent manifestation. These five syndromes differ markedly in their etiologies and clinical features, and were selected for discussion because the seizures are generated at a different 'level' of neural dysfunction in each case: (1) mutation of a specific family of ion (potassium) channels in benign familial neonatal convulsions; (2) deficiency of the protein that transports glucose into the CNS in Glut-1 deficiency; (3) aberrantly formed local neural circuits in focal cortical dysplasia; (4) synaptic reorganization of limbic circuitry in temporal lobe epilepsy; and (5) abnormal thalamocortical circuit function in childhood absence epilepsy. Despite this diversity of clinical phenotype and mechanism, these syndromes are informative as to how pathophysiological processes converge to produce brain hyperexcitability and seizures.
J Cereb Blood Flow Metab 2006 Aug
PMID:Epilepsy: a review of selected clinical syndromes and advances in basic science. 1643 61

We investigated the dependency of electrical seizures produced by cortical undercut upon behavioral states of vigilance in chronically implanted cats. Experiments were performed 1-12 weeks after white matter transection. Multisite field potentials and intracellular activity were recorded from suprasylvian and marginal gyri. Paroxysmal activity developed within days and consisted of spike-wave complexes at 3-4 Hz occurring during the waking state (correlated with eye movements), being enhanced during slow-wave sleep (SWS) and blocked during rapid eye movement (REM) sleep. Prolonged hyperpolarizing events were seen not only during SWS (which is the case in normal animals) but also during both waking and REM, thus resulting in bimodal distribution of the membrane potential in all 3 natural states of vigilance. The increased synchrony of field potential activity expressed by shorter time of propagation over the cortical surface and the tendency toward generalization are ascribed to changes in intrinsic neuronal properties and potential disinhibition following cortical undercut.
Cereb Cortex 2007 Feb
PMID:Waking-sleep modulation of paroxysmal activities induced by partial cortical deafferentation. 1649 31

Disturbances in GABAergic and glutamatergic neurotransmission in the thalamocortical loop are involved in absence seizures. Here, we examined potential disturbances in metabolism and interactions between neurons and glia in 5-month-old genetic absence epilepsy rats from Strasbourg (GAERS) and nonepileptic rats (NER). Animals received [1-(13)C]glucose and [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex, thalamus, and hippocampus were analyzed by (13)C nuclear magnetic resonance spectroscopy. Most changes were detected in the cortex. Pyruvate metabolism was enhanced as evidenced by increases of lactate, and labeled and unlabeled alanine. Neuronal mitochondrial metabolism was also enhanced as detected by elevated amounts of N-acetylaspartate and nicotinamide adenine dinucleotide as well as increased incorporation of label from [2-(13)C]acetyl CoA into glutamate, glutamine, and aspartate. Likewise, mitochondrial metabolism in astrocytes was increased. Changes in thalamus were restricted to increased concentration and labeling of glutamine. Changes in the hippocampus were similar to those in the cortex. This increase in glutamate-glutamine metabolism in cortical neurons and astrocytes accompanied by a decreased gamma aminobyturic acid level may lead to impaired thalamic filter function. Hence, reduced sensory input to cortex could allow the occurrence of spike-and-wave discharges in the thalamocortical loop. Increased glutamatergic output from the cortex to hippocampus may be the underlying cause of improved learning in GAERS.
J Cereb Blood Flow Metab 2006 Dec
PMID:Cortical glutamate metabolism is enhanced in a genetic model of absence epilepsy. 1653 29

The physiological conditions that swell mammalian neurons are clinically important but contentious. Distinguishing the neuronal component of brain swelling requires viewing intact neuronal cell bodies, dendrites, and axons and measuring their changing volume in real time. Cultured or dissociated neuronal somata swell within minutes under acutely overhydrated conditions and shrink when strongly dehydrated. But paradoxically, most central nervous system (CNS) neurons do not express aquaporins, the membrane channels that conduct osmotically driven water. Using 2-photon laser scanning microscopy (2PLSM), we monitored neuronal volume under osmotic stress in real time. Specifically, the volume of pyramidal neurons in cerebral cortex and axon terminals comprising cerebellar mossy fibers was measured deep within live brain slices. The expected swelling or shrinking of the gray matter was confirmed by recording altered light transmittance and by indirectly measuring extracellular resistance over a wide osmotic range of -80 to +80 milliOsmoles (mOsm). Neurons expressing green fluorescent protein were then imaged with 2PLSM between -40 and +80 mOsm over 20 min. Surprisingly, pyramidal somata, dendrites, and spines steadfastly maintained their volume, as did the cerebellar axon terminals. This precluded a need for the neurons to acutely regulate volume, preserved their intrinsic electrophysiological stability, and confirmed that these CNS nerve cells lack functional aquaporins. Thus, whereas water easily permeates the aquaporin-rich endothelia and glia driving osmotic brain swelling, neurons tenatiously maintain their volume. However, these same neurons then swell dramatically upon oxygen/glucose deprivation or [K+]0 elevation, so prolonged depolarization (as during stroke or seizure) apparently swells neurons by opening nonaquaporin channels to water.
Cereb Cortex 2007 Apr
PMID:Physiological evidence that pyramidal neurons lack functional water channels. 1672 8

Long-term video electroencephalographic (EEG) recording is currently a routine procedure in the presurgical evaluation of localization-related epilepsies. Cortical epileptogenic zone is usually localized from ictal recordings with intracranial electrodes, causing a significant burden to patients and health care. Growing literature suggests that epileptogenic networks exhibit aberrant dynamics also during seizure-free periods. We examined if neocortical epileptogenic regions can be circumscribed by quantifying local long-range temporal (auto-)correlations (LRTC) with detrended fluctuation analysis of seizure-free ongoing subdural EEG activity in 4 frequency bands in 5 patients. We show here with subdural EEG recordings that the LRTC are abnormally strong near the seizure onset area. This effect was most salient in neocortical oscillations in the beta frequency band (14-30 Hz). Moreover, lorazepam, a widely used antiepileptic drug, exerted contrasting effects on LRTC (n = 2): lorazepam attenuated beta-band LRTC near the epileptic focus, whereas it strengthened LRTC in other cortical areas. Our findings demonstrate that interictal neuronal network activity near the focus of seizure onset has pathologically strong intrinsic temporal correlations. The observed effect by lorazepam on beta-band activity suggests that the antiepileptic mechanism of benzodiazepines may be related to the normalization of LRTC within the epileptic focus. We propose that this method may become a promising candidate for routine invasive and noninvasive presurgical localization of epileptic foci.
Cereb Cortex 2007 Jun
PMID:Epileptogenic neocortical networks are revealed by abnormal temporal dynamics in seizure-free subdural EEG. 1690 92

We mapped the profile of neocortical thickness and complexity in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Thirty preoperative high-resolution magnetic resonance imaging scans were acquired from 15 right (mean age: 31.9 +/- 9.7 standard deviation [SD] years) and 15 left (mean age: 30.8 +/- 8.4 SD years) MTLE patients who were seizure-free for 2 years after anteriomesial temporal resection. Nineteen healthy controls were also scanned (mean age: 24.8 +/- 3.9 SD years). A cortical pattern matching technique mapped thickness across the entire neocortex. Mesial temporal structures were not included in this analysis. Cortical models were remeshed in frequency space to compute their fractal dimension (surface complexity). Both MTLE groups showed up to 30% bilateral decrease in cortical thickness, in the frontal poles, frontal operculum, orbitofrontal, lateral temporal, and occipital regions. In both groups, cortical complexity was decreased in multiple lobar regions. Significant linkages were found relating longer duration of epilepsy to greater cortical thickness reduction in the superior frontal and parahippocampal gyrus ipsilateral to the side of seizure onset. The pervasive extrahippocampal structural deficits may result from chronic seizure propagation or may reflect other causes such as initial precipitating factors leading to MTLE.
Cereb Cortex 2007 Sep
PMID:Reduced neocortical thickness and complexity mapped in mesial temporal lobe epilepsy with hippocampal sclerosis. 1708 74

During intense cerebral activation approximately half of the glucose plus lactate taken up by the human brain is not oxidized and could replenish glycogen deposits, but the human brain glycogen concentration is unknown. In patients with temporal lobe epilepsy, undergoing curative surgery, brain biopsies were obtained from pathologic hippocampus (n=19) and from apparently 'normal' cortical grey and white matter. We determined the in vivo brain glycogen level and the activity of glycogen phosphorylase and synthase. Regional differences in glycogen concentration were examined similarly in healthy pigs (n=5). In the patients, the glycogen concentration in 'normal' grey and white matter was 5 to 6 mmol/L, but much higher in the hippocampus, 13.1+/-4.3 mmol/L (mean+/-s.d.; P<0.001); the activities of glycogen phosphorylase and synthase displayed the same pattern. In normal hippocampus from pigs, glycogen was similarly higher than in grey and white matter. Consequently, in human grey and white matter and, particularly, in the hippocampus of patients with temporal lope epilepsy, glycogen constitutes a large, active energy reserve, which may be of importance for energy provision during sustained synaptic activity as epileptic seizures.
J Cereb Blood Flow Metab 2007 Jun
PMID:High glycogen levels in the hippocampus of patients with epilepsy. 1713 25


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