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

The "dormant basket cell" hypothesis suggests that postinjury hippocampal network hyperexcitability results from the loss of vulnerable neurons that normally excite insult-resistant inhibitory basket cells. We have reexamined the experimental basis of this hypothesis in light of reports that excitatory hilar mossy cells are not consistently vulnerable and inhibitory basket cells are not consistently seizure resistant. Prolonged afferent stimulation that reliably evoked granule cell discharges always produced extensive hilar neuron degeneration and immediate granule cell disinhibition. Conversely, kainic acid-induced status epilepticus in chronically implanted animals produced similarly extensive hilar cell loss and immediate granule cell disinhibition, but only when granule cells discharged continuously during status epilepticus. In both preparations, electron microscopy revealed degeneration of presynaptic terminals forming asymmetrical synapses in the mossy cell target zone, including some terminating on gamma-aminobutyric acid-immunoreactive elements, but no evidence of axosomatic or axoaxonic degeneration in the adjacent granule cell layer. Although parvalbumin immunocytochemistry and in situ hybridization revealed decreased staining, this apparently was due to altered parvalbumin expression rather than basket cell death, because substance P receptor-positive interneurons, some of which contained residual parvalbumin immunoreactivity, survived. These results confirm the inherent vulnerability of dendritically projecting hilar mossy cells and interneurons and the relative resistance of dentate inhibitory basket and chandelier cells that target granule cell somata. The variability of hippocampal cell loss after status epilepticus suggests that altered hippocampal structure and function cannot be assumed to cause the spontaneous seizures that develop in these animals and highlights the importance of confirming hippocampal pathology and pathophysiology in vivo in each case.
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PMID:"Dormant basket cell" hypothesis revisited: relative vulnerabilities of dentate gyrus mossy cells and inhibitory interneurons after hippocampal status epilepticus in the rat. 1262 66

Interstitial deletion on chromosome 5q33.3q35.1 is an extremely rare chromosomal aberration for which a characteristic syndrome could not yet be delineated. In most patients with 5q deletions severe mental retardation is described. Recently, Spranger et al. (2000) described the case of a 4-year-old girl with a de novo deletion on 5q33.3q35.1 presenting only with mild psychomotor delay, minor facial anomalies, and seizures. The patient was admitted for outpatient neuropsychological assessment when she was 6.2 years old. Neurocognitive tests revealed an overall developmental delay of about 32 months and an intelligence score in the range of mild mental retardation. Her cognitive phenotype was characterized by a considerable visual-spatial deficit in the form of disorganized drawings or block designs indicating a profound lack of cohesion and overall global organization (decay of gestalt). The patient's behavioral phenotype was dominated by a distinct disinhibition syndrome demonstrating severe hyperactivity, utilization behavior, and aggressive behavior.
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PMID:Interstitial deletion on chromosome 5q33.3q35.1 in a 6-year-old girl -- neuropsychological findings and follow-up in an extremely rare chromosomal aberration. 1281 15

Urethral masturbation and sexual disinhibition as manifestations of behavioral and psychological symptoms of dementia (BPSD) are described in a 90-year-old patient who repeatedly self-inserted foreign bodies into his urethra. A diagnosis was made of late onset sexual disinhibition and hypersexuality in a patient with Dementia of the Alzheimer Type. Significant reduction of his sexual behavior was achieved with low doses of haloperidol. Similar symptoms are noted in Pick's disease, other fronto-temporal lesions, mania and following a seizure or treatment of Parkinson's disease, and have been described as Kluver-Busy-type. Clinicians should consider this diagnosis when investigating dysuria, cystitis, haematuria and urinary tract infections even in the very old.
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PMID:Urethral masturbation and sexual disinhibition in dementia: a case report. 1281 71

We investigated the nicotinic modulation of the excitatory field potentials recorded from the immature (postnatal day 10-20) hippocampal CA3 area, in the presence of the GABA(A) antagonist bicuculline methiodide (BMI, 10 microM). Nicotine (50 microM) enhanced the evoked field potentials; its effects were also observed in the presence of the GABA(B) antagonist 2-hydroxy-saclofen (250 microM; added to BMI) and were blocked by pre-perfusion with the nicotinic antagonist hexamethonium (HXM, 50 microM). The potentiating effects of nicotine in BMI persisted during prolonged perfusion (more than 20 min), while those in control perfusion medium were transient. The nicotinic antagonists HXM (50 microM), methyllycaconitine (MLA, 0.01 microM) and dihydro-beta-erythroidine (DHbetaE, 50 microM) potentiated CA3-evoked field potentials. Perfusion of HXM in the presence of the anticholinesterase eserine (1 microM) or the muscarinic antagonist atropine (1 microM) did not alter its effects. None of the nicotinic agents tested changed the frequency of spontaneous BMI-induced epileptiform discharges (nicotine, HXM, MLA, DhbetaE), suggesting that nicotinic receptors do not drive spontaneous epileptiform discharges in this in vitro model. These experiments demonstrate that nicotinic receptors are activated tonically during disinhibition and modulate the activity of excitatory synapses in the immature CA3 hippocampal area. The persistent nicotinic facilitatory effects during disinhibition versus the transient in control conditions indicate that nicotinic modulation depends on environmental conditions and also that nicotinic receptors may be a contributing factor in early-life seizures.
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PMID:Nicotinic effects on excitatory field potentials recorded from the immature CA3 area of rat hippocampal slices. 1289 92

Cortical trauma can lead to development of electrographic paroxysmal activities. Current views of trauma-induced epileptogenesis suggest that chronic neuronal hyperexcitability and extensive morphological reorganization of the traumatized cortex are required for the generation of electrographic seizures. However, the mechanisms responsible for the initiation of electrographic seizures shortly after cortical injury are poorly understood. Here we show that, in the experimental model of partially deafferented (undercut) cortex, an increase in intrinsic and synaptic excitability of neurons in areas adjacent to the undercut cortex is sufficient for the generation of electrographic paroxysmal activity within few hours after partial cortical deafferentation. Locally increased and spatially restricted neuronal excitability arose from the increased incidence of intrinsically bursting neurons, enhanced intrinsic and synaptic neuronal responsiveness, and slight disinhibition. These mechanisms only operate in neurons located in the vicinity of partially deafferented sites because, after the cortical injury, partially deafferented neurons are mostly silent and hypoexcitable. Our results suggest that trauma-induced electrographic seizures first arise in cortical fields that are closest to the site of injury and such seizures do not require long-term neuronal reorganization.
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PMID:Hyperexcitability of intact neurons underlies acute development of trauma-related electrographic seizures in cats in vivo. 1291 45

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.
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PMID:Optical imaging of epileptiform events in visual cortex in response to patterned photic stimulation. 1461 95

CNS drugs may act by modifying the emergent properties of complex CNS neuronal networks. Emergent properties are network characteristics that are not predictably based on properties of individual member neurons. Neuronal membership within networks is controlled by several mechanisms, including burst firing, gap junctions, endogenous and exogenous neuroactive substances, extracellular ions, temperature, interneuron activity, astrocytic integration and external stimuli. The effects of many CNS drugs in vivo may critically involve actions on specific brain loci, but this selectivity may be absent when the same neurons are isolated from the network in vitro where emergent properties are lost. Audiogenic seizures (AGS) qualify as an emergent CNS property, since in AGS the acoustic stimulus evokes a non-linear output (motor convulsion), but the identical stimulus evokes minimal behavioral changes normally. The hierarchical neuronal network, subserving AGS in rodents is initiated in inferior colliculus (IC) and progresses to deep layers of superior colliculus (DLSC), pontine reticular formation (PRF) and periaqueductal gray (PAG) in genetic and ethanol withdrawal-induced AGS. In blocking AGS, certain anticonvulsants reduce IC neuronal firing, while other agents act primarily on neurons in other AGS network sites. However, the NMDA receptor channel blocker, MK-801, does not depress neuronal firing in any network site despite potently blocking AGS. Recent findings indicate that MK-801 actually enhances firing in substantia nigra reticulata (SNR) neurons in vivo but not in vitro. Thus, the MK-801-induced firing increases in SNR neurons observed in vivo may involve an indirect effect via disinhibition, involving an action on the emergent properties of this seizure network.
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PMID:Emergent properties of CNS neuronal networks as targets for pharmacology: application to anticonvulsant drug action. 1501 76

This review focuses on the remodeling of brain circuitry associated with epilepsy, particularly in excitatory glutamate and inhibitory GABA systems, including alterations in synaptic efficacy, growth of new connections, and loss of existing connections. From recent studies on the kindling and status epilepticus models, which have been used most extensively to investigate temporal lobe epilepsy, it is now clear that the brain reorganizes itself in response to excess neural activation, such as seizure activity. The contributing factors to this reorganization include activation of glutamate receptors, second messengers, immediate early genes, transcription factors, neurotrophic factors, axon guidance molecules, protein synthesis, neurogenesis, and synaptogenesis. Some of the resulting changes may, in turn, contribute to the permanent alterations in seizure susceptibility. There is increasing evidence that neurogenesis and synaptogenesis can appear not only in the mossy fiber pathway in the hippocampus but also in other limbic structures. Neuronal loss, induced by prolonged seizure activity, may also contribute to circuit restructuring, particularly in the status epilepticus model. However, it is unlikely that any one structure, plastic system, neurotrophin, or downstream effector pathway is uniquely critical for epileptogenesis. The sensitivity of neural systems to the modulation of inhibition makes a disinhibition hypothesis compelling for both the triggering stage of the epileptic response and the long-term changes that promote the epileptic state. Loss of selective types of interneurons, alteration of GABA receptor configuration, and/or decrease in dendritic inhibition could contribute to the development of spontaneous seizures.
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PMID:Kindling and status epilepticus models of epilepsy: rewiring the brain. 1519 78

The effects of the A(3) adenosine receptor agonist 2-Cl-IB-MECA were tested on epileptiform field potentials recorded in the CA3 area of postnatal days 10-20 immature hippocampal slices, during perfusion with the GABA(A) receptor antagonist bicuculline (10 microM). Evoked potentials: 2-Cl-IB-MECA (1-50 microM, n = 17) had consistently excitatory effects, blocked by the A(3) receptor antagonist MRS 1220 (1 microM, n = 7), but not occluded in the presence of the A(1) antagonist DPCPX (1 microM, n = 12) or the A(2A) antagonist ZM-241385 (0.1 microM, n = 12). 2-Cl-IB-MECA reversed the inhibitory effects (n = 5) of the adenosine uptake blocker nitrobenzylthioinosine (NBTI, 50 microM), but did not increase its excitatory effects (n = 19). Spontaneous discharges: 2-Cl-IB-MECA (1 microM) induced them or increased their frequency in 14/30 slices, an effect reversed by MRS 1220 (n = 3), and observed also following pre-perfusion with DPCPX (n = 11), ZM-241385 (n = 11) or both (n = 10). In the presence of the A(1) antagonist DPCPX, NBTI increased the frequency of spontaneous discharges, an effect partially reversed by MRS 1220 (n = 8), thus suggesting that a rise in endogenous adenosine during disinhibition may activate A(3) receptors. In conclusion, these findings suggest strongly that activation of A(3) receptors, following a rise in endogenous adenosine (i.e. during seizures, hypoxia), facilitates excitation, thus limiting the known inhibitory and/or neuroprotective effects of adenosine in immature brain.
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PMID:The A3 adenosine receptor agonist 2-Cl-IB-MECA facilitates epileptiform discharges in the CA3 area of immature rat hippocampal slices. 1524 13

Memory impairment is a common consequence of epileptic seizures. The hippocampal formation is particularly prone to seizure-induced amnesia due to its prominent role in mnemonic processes. We used the isolated CA1 slice preparation to examine effects of seizure-like activity on hippocampal plasticity, long-term potentiation (LTP), and long-term depression (LTD). Repeated spontaneous ictal events, generated in the presence of antagonists of GABA(A) receptor function, led to a stepwise erasure of LTP (termed spontaneous depotentiation, SDP). SDP could be initiated at various stages of LTP consolidation (tested < or =120 min after the induction of LTP). Renewed tetanic stimulation re-established LTP. SDP was remarkably specific: baseline transmission and other forms of hippocampal plasticity, i.e., Ca(2+)-induced LTP and two forms of LTD [(RS)-3,5-dihydroxyphenyglycine (DHPG) mediated and low-frequency stimulation mediated] were not affected by the same type of seizure activity. SDP was blocked in the presence of the group I mGluR antagonist (S)-4-carboxyphenylglycine. The mGluR1 antagonist (S)-(+)-alpha-amino-methylbenzeneacetic acid blocked approximately 80%, the mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)-pyridine approximately 30% of SDP. Most efficient implementation of SDP was observed during seizures in the combined presence of the group I mGluR agonist DHPG and the GABA(A) antagonist bicuculline. However, similar ictal activity generated in the presence of DHPG alone did not lead to SDP in the vast majority of recordings. Complete disinhibition and at least partial activation of group I mGluR were necessary conditions for the induction of SDP. The depotentiating pharmacological conditions were accompanied by tonic membrane depolarization of CA1 pyramidal cells. Since hyperpolarization (by negative current injection) prevented intracellular SDP under depotentiating pharmacological conditions and depolarization (by positive current injection) led to selective intracellular SDP in the non-depotentiating seizure protocol of DHPG, it is concluded that cell depolarization was a sufficient condition for seizure-like activity to reverse hippocampal LTP.
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PMID:Reversal of hippocampal LTP by spontaneous seizure-like activity: role of group I mGluR and cell depolarization. 1528 58


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