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

Metabotropic glutamate (mGlu) receptors have been considered as potential targets for neuroprotective drugs, but the lack of specific drugs has limited the development of neuroprotective strategies in experimental models of acute or chronic central nervous system (CNS) disorders. The advent of potent and centrally available subtype-selective ligands has overcome this limitation, leading to an extensive investigation of the role of mGlu receptor subtypes in neurodegeneration during the last 2 years. Examples of these drugs are the noncompetitive mGlu1 receptor antagonists, CPCCOEt and BAY-36-7620; the noncompetitive mGlu5 receptor antagonists, 2-methyl-6-(phenylethynyl)pyridine, SIB-1893, and SIB-1757; and the potent mGlu2/3 receptor agonists, LY354740 and LY379268. Pharmacologic blockade of mGlu1 or mGlu5 receptors or pharmacologic activation of mGlu2/3 or mGlu4/7/8 receptors produces neuroprotection in a variety of in vitro or in vivo models. MGlu1 receptor antagonists are promising drugs for the treatment of brain ischemia or for the prophylaxis of neuronal damage induced by synaptic hyperactivity. MGlu5 receptor antagonists may limit neuronal damage induced by a hyperactivity of N-methyl-d-aspartate (NMDA) receptors, because mGlu5 and NMDA receptors are physically and functionally connected in neuronal membranes. A series of observations suggest a potential application of mGlu5 receptor antagonists in chronic neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer disease. MGlu2/3 receptor agonists inhibit glutamate release, but also promote the synthesis and release of neurotrophic factors in astrocytes. These drugs may therefore have a broad application as neuroprotective agents in a variety of CNS disorders. Finally, mGlu4/7/8 receptor agonists potently inhibit glutamate release and have a potential application in seizure disorders. The advantage of all these drugs with respect to NMDA or AMPA receptor agonists derives from the evidence that mGlu receptors do not "mediate," but rather "modulate" excitatory synaptic transmission. Therefore, it can be expected that mGlu receptor ligands are devoid of the undesirable effects resulting from the inhibition of excitatory synaptic transmission, such as sedation or an impairment of learning and memory.
J Cereb Blood Flow Metab 2001 Sep
PMID:Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs. 1152 8

The projections from the amygdaloid complex to the hippocampus and surrounding cortex have a critical role in the formation of memories for emotionally arousing stimuli and in the spread of epileptic seizures. The present study investigated the organization of amygdaloid projections to the perirhinal and postrhinal cortices by injecting the anterograde tracer Phaseolus vulgaris leucoagglutinin into the different subdivisions of the lateral, basal or accessory basal nuclei of the amygdala in rat (n = 53). Analysis of immunohistochemically stained sections indicated that the medial and dorsolateral divisions of the lateral nucleus project heavily to layers I-V of caudal area 35 and to layers I-III of the rostroventral postrhinal cortex. The dorsolateral division also moderately innervates layer I of caudoventral area 36. The magnocellular division of the basal nucleus projects moderately to layers V and VI of rostral areas 35 and 36. The parvicellular division of the accessory basal nucleus projects moderately to layer V of caudal area 35, whereas the magnocellular division projects moderately to layers I and II of rostral area 35. Via these substantial, topographically organized projections, the amygdaloid complex might modulate information processing at different levels of the medial temporal lobe memory system.
Cereb Cortex 2001 Nov
PMID:Projections from the lateral, basal and accessory basal nuclei of the amygdala to the perirhinal and postrhinal cortices in rat. 1159 Jan 16

The effect of experimentally induced seizure activity on the functional reorganization of motor maps has not previously been investigated. Furthermore, while the functional reorganization of motor maps has been thought to involve increases in synaptic communication, there has yet to be a test of this hypothesis. Here we show that repeated seizure activity (kindling), that is accompanied by increased synaptic strength within adult rat motor cortex, results in a doubling of the caudal forelimb motor area. We measured neo-cortical evoked potentials in the right hemisphere prior to 25 days of electrical kindling of the medial frontal corpus callosum or amygdala and re-measured them either 1 or 21 days following the last kindling session. Then, using high resolution intracortical microstimulation (ICMS), the caudal forelimb area in the left hemisphere was mapped. This is the first report of any procedure causing a motor representation to double in size. Furthermore, this expansion was related to the enhanced area of a neocortical polysynaptic field potential and not the motor convulsions per se. Moreover, both the motor map and field potential enhancements were persistent in nature and could be driven from either cortical or limbic sites. The data have implications for human populations with epilepsy.
Cereb Cortex 2002 Jan
PMID:Motor map expansion following repeated cortical and limbic seizures is related to synaptic potentiation. 1173 36

Epilepsias are chronic central nervous system diseases which manifest by recurrent seizures. They may be classified into channelopathies resulting from mutations of ionic channels or receptors for neurotransmitters, and epilepsias which are secondary to cortical damage and result from the reconstruction of cortical neural networks. Chronic or generalized seizures initiate processes called the "excititoxic cascade" the effector side of which, quite similar to that of the "ischemic cascade", may lead to neuronal death through either apoptosis or necrosis. Therefore, complementing pharmacological treatment of epilepsia with neuroprotective substances such as free radical scavenger or CDP-choline which blocks the activation of phospholipase A2 may be indicated.
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PMID:[The mechanisms of neuronal death and advances in the neural protection in epilepsy]. 1178 May 93

Coupling between local cerebral blood flow and local cerebral metabolic rate for glucose is involved in the pathogenesis of epilepsy-related neuronal damage in the adult brain; however, its role in the immature brain is unknown. Lithium-pilocarpine-induced status epilepticus is associated with extended damage in adult rats, mostly in the forebrain limbic areas and thalamus, whereas damage was moderate in 21-day-old rats (P21) or absent in P10 rats. The quantitative autoradiographic [14C]iodoantipyrine technique was applied to measure the consequences of lithium-pilocarpine status epilepticus on local cerebral blood flow. In adult and P21 rats, local cerebral blood flow rates increased by 50% to 400%; the highest increases were recorded in regions showing damage in adults. At P10, local cerebral blood flow rates decreased by 40% to 60% in most areas, except in some forebrain regions showing no change during status epilepticus. In areas injured when status epilepticus was induced in adults, a strong hypermetabolism (Fernandes et al., 1999) not matched by comparable local cerebral blood flow increases was present in rats of all ages, whereas in damage-resistant areas, local cerebral metabolic rate for glucose and local cerebral blood flow remained coupled in the three age groups. Thus, the level of coupling between blood flow supply and metabolism is not involved in seizure-related brain damage in the developing brain, which appears to be resistant to the consequences of such a mismatch.
J Cereb Blood Flow Metab 2002 Feb
PMID:Local cerebral blood flow during lithium-pilocarpine seizures in the developing and adult rat: role of coupling between blood flow and metabolism in the genesis of neuronal damage. 1182 17

Increasing evidence suggests that glial cells are endowed with the ability to externalize their activity to the extracellular space and to neurons. Since the same activity is influenced by the extracellular ionic concentrations and the neurotransmitters released by neurons, it is suggested that neurons and glia entertain a continuous exchange of information. This behavior might have a particular significance during cortical oscillations. In this study we analyzed the time and voltage relationships within simultaneously recorded neuron-glia pairs during normal states characterized by a slow (<1 Hz) sleep oscillation and during paroxysmal epileptic discharges. Our data show that cortical neurons and glia display coherent activities during the tested spontaneous oscillations. The onset of the depolarizing phase of the slow oscillation started in neurons and followed with a lag of 88 ms in nearby (1-2 mm) recorded glial cells. In contrast, the beginning of the hyperpolarizing phase was initiated in glial cells, and neurons followed after 79 ms, suggesting that glial activities are not exclusively the reflection of neuronal ones. Moreover, we tested neuronal excitability that resulted in phase opposition with the glial membrane potential, establishing that only the first 30% of the neuronal depolarization is efficient for synaptic volleys within cortical neuronal networks. Seizures were associated with shorter time lags at onset of depolarization (1.8 ms) and with delayed glial offset (102 ms). The voltage slope and amplitude at the onset of the paroxysmal depolarizations were higher than in the case of the slow oscillation. Together with the variation of neuronal excitability, these results suggest that the glial uptake of K(+) contributes to the abridged duration of the paroxysmal depolarization.
Cereb Cortex 2002 Oct
PMID:Glial and neuronal interactions during slow wave and paroxysmal activities in the neocortex. 1221 74

This study determined whether stroke and other types of insults produced a gene expression profile in blood that correlated with the presence of neuronal injury. Adult rats were subjected to ischemic stroke, intracerebral hemorrhage, status epilepticus, and insulin-induced hypoglycemia and compared with untouched, sham surgery, and hypoxia animals that had no brain injury. One day later, microarray analyses showed that 117 genes were upregulated and 80 genes were downregulated in mononuclear blood cells of the "injury" (n = 12) compared with the "no injury" (n = 9) animals. A second experiment examined the whole blood genomic response of adult rats after global ischemia and kainate seizures. Animals with no brain injury were compared with those with brain injury documented by TUNEL and PANT staining. One day later, microarray analyses showed that 37 genes were upregulated and 67 genes were downregulated in whole blood of the injury (n = 4) animals compared with the no-injury (n = 4) animals. Quantitative reverse transcription-polymerase chain reaction confirmed that the vesicular monoamine transporter-2 increased 2.3- and 1.6-fold in animals with severe and mild brain injury, respectively, compared with no-injury animals. Vascular tyrosine phosphatase-1 increased 2.0-fold after severe injury compared with no injury. The data support the hypothesis that there is a peripheral blood genomic response to neuronal injury, and that this blood response is associated with a specific blood mRNA gene expression profile that can be used as a marker of the neuronal damage.
J Cereb Blood Flow Metab 2003 Mar
PMID:Blood genomic expression profile for neuronal injury. 1262 6

Disturbed glucose brain metabolism after brain trauma is reflected by changes in extracellular glucose levels. The authors hypothesized that posttraumatic reductions in extracellular glucose levels are not due to ischemia and are associated with poor outcome. Intracerebral microdialysis, electroencephalography, and measurements of brain tissue oxygen levels and jugular venous oxygen saturation were performed in 30 patients with traumatic brain injury. Levels of glucose, lactate, pyruvate, glutamate, and urea were analyzed hourly. The 6-month Glasgow Outcome Scale extended (GOSe6) score was assessed for each patient. In regions of increased glucose utilization defined by positron emission tomography, the extracellular glucose concentration was less than 0.2 mmol/l. Extracellular glucose values were less than 0.2 mmol during postinjury days 0 to 7 in 19% to 30% of hourly samples on each day. Transient decreases in glucose levels occurred with electrographic seizures and nonischemic reductions in cerebral perfusion pressure and jugular venous oxygen saturation. Glutamate levels were elevated in the majority of low-glucose samples, but the lactate/pyruvate ratio did not indicate focal ischemia. Terminal herniation resulted in reductions in glucose with increases in the lactate/pyruvate ratio but not in lactate concentration alone. GOSe6 scores correlated with persistently low glucose levels, combined early low glucose levels and low lactate/glucose ratio, and with the overall lactate/glucose ratio. These results suggest that the level of extracellular glucose is typically reduced after traumatic brain injury and associated with poor outcome, but is not associated with ischemia.
J Cereb Blood Flow Metab 2003 Jul
PMID:Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. 1284 90

This study tested the hypothesis that early functional alterations in neuronal synchrony in the partially deafferented cortex may lead to spontaneously occurring electrographic seizures. In vivo experiments with partial deafferentation of cat suprasylvian gyrus after extensive undercut of the white matter were conducted using multi-site EEG, extracellular unit and intracellular recordings. The amplitudes of EEG waves were much higher in the areas surrounding deafferented cortical fields as compared with control and with undercut cortex. In 40% of animals with undercut cortex, paroxysmal activity occurred 2-3 h after the undercut and was initiated in the relatively intact cortex, adjacent to the more disconnected one. The seizures that followed the undercut consisted of spike-wave/polyspike-wave complexes and fast runs, resembling the electrographic patterns of some clinical epileptic syndromes. An increased local synchrony in the relatively intact cortex evolved into paroxysmal activity that ultimately spread to the deafferented cortex. The electrographic seizures were found only in animals that showed a propagation of the slow sleep-like oscillation in control conditions. The increase of long-range synchrony within a given seizure was associated with seizure termination. These results indicate that alterations in neuronal synchrony following neuronal trauma can be a critical factor triggering electrographic seizures.
Cereb Cortex 2003 Aug
PMID:Partial cortical deafferentation promotes development of paroxysmal activity. 1285 75

In a subset of patients with epilepsy, patterned visual stimuli can trigger clinical seizures. The etiology of this phenomenon, and the complex interaction between functional architecture and epilepsy, were investigated in ferret visual cortex. Optical imaging of intrinsic signals was used to visualize maps of orientation, ocular dominance and spatial frequency. Acute interictal spike foci were then induced within V1 using focal iontophoresis of bicuculline methiodide and optically mapped during presentation of patterned visual stimuli. We found that specific orientations and spatial frequencies could preferentially trigger epileptiform events, depending on the location of the epicenter of the epileptic focus within the columnar architecture of visual cortex. These data support a cortical etiology of the clinical phenomenon of pattern-sensitive epilepsy. We were not able to demonstrate a spatial correlation between the functional architecture maps and the topography of the epileptic focus. These findings implicate short-range rather than long-range horizontal excitatory connections in the lateral spread of interictal spikes, which may be specific to the epilepsy model of acute focal disinhibition. Orientation and spatial frequency maps were severely disturbed in the region of the focus but were unaltered in the surrounding cortex. Thus, optical imaging of intrinsic signals can be used to simultaneously map epilepsy and normal functional anatomy with high spatial resolution.
Cereb Cortex 2003 Dec
PMID:Optical imaging of epileptiform events in visual cortex in response to patterned photic stimulation. 1461 95


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