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

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.
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PMID:Mechanisms in the development of limbic status epilepticus and hippocampal neuron loss: an experimental study in a model of status epilepticus induced by kindling-like electrical stimulation of the deep prepyriform cortex in rats. 153 85

Hippocampal CA3 pyramidal neurons in the adult epileptic mutant mouse tottering (tg) show normal intrinsic membrane properties, yet fire abnormally prolonged paroxysmal depolarizing shifts (PDS) during in vitro exposure to elevated extracellular potassium solutions. Intracellular recordings in immature mutants reveal that this network burst abnormality is present during the developmental period that coincides with the onset of seizures in the mutant (19-20 postnatal days), and is significantly more pronounced at this age than at adulthood. These data are inconsistent with the hypothesis that the mutant PDS prolongation represents a secondary consequence of a prolonged history of repeated seizures and suggest that it may reflect a cellular epileptogenic phenotype more directly related to the primary neuropathological expression of the tg gene.
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PMID:A burst-dependent hippocampal excitability defect elicited by potassium at the developmental onset of spike-wave seizures in the Tottering mutant. 157 65

Acute and chronic effects of seizures induced by intraperitoneal (i.p.) injection of kainic acid (KA) were studied in developing rats (postnatal days (P) 5, 10, 20, 30, and adult 60). For 3 months following KA-induced status epilepticus, spontaneous recurrent seizure (SRS) occurrence was quantified using intermittent video monitoring. Latency to generalized seizures was then tested using flurothyl, and brains were histologically analyzed for CA3 lesions. In P5-10 rats, KA caused generalized tonic-clonic ('swimming') seizures. SRS did not develop, and there was no significant difference between control and KA-treated rats in latency to flurothyl-induced seizures. In contrast, rats P20 and older exhibited limbic automatisms followed by limbic motor seizures which secondarily generalized. Incidence and frequency of SRS increased with age. P20-30 rats with SRS had shorter latencies to flurothyl seizures than did KA-treated P20-30 rats without SRS or controls. KA-treated P60 rats (with or without SRS) had shorter latencies than controls to flurothyl seizure onset. SRS in P60 rats occurred sooner after KA than in P20-30 rats. CA3 lesions were seen in P20-60 rats with and without SRS, but not in P5-10 rats. These data suggest that there are developmental differences in both acute and chronic responses to KA, with immature animals relatively protected from the long-term deleterious effects of this convulsant.
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PMID:Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures. 157 66

Immunocytochemistry with specific antisera was used to assess regional levels of six immediate early gene encoded proteins (KROX-24, c-FOS, FOS B, c-JUN, JUN B and JUN D) in the rat hippocampus after 15 min of bicuculline-induced seizures. Serial sections of the dorsal hippocampus were examined at various postictal recovery periods up to 24 h. The results demonstrate a complex temporal and spatial pattern of immediate early gene synthesis and accumulation. Three major categories of immediate early gene products could best be distinguished in the dentate gyrus: KROX-24 and c-FOS showed a concurrent rapid rise with peak levels at 2 h and a return to baseline levels within 8 h after seizure termination. FOS B, c-JUN and JUN B levels increased more gradually with peak intensities in the dentate gyrus reached at 4 h. These immediate early gene products showed above normal levels in various hippocampal subpopulations up to 24 h. JUN D exhibited the most delayed onset combined with a prolonged increase of seizure-induced immunoreactivity. Irrespective of this differential temporal expression profile of individual transcription factors, the sequence of induction in the hippocampal subpopulations was identical for all immediate early gene-encoded proteins examined: first in the dentate gyrus granule cells followed by CA1 and CA3 neurons, respectively. Our data indicate an asynchronous synthesis of several immediate early gene-encoded proteins in the brain after status epilepticus. FOS and JUN proteins act via homo- or heterodimer complexes at the AP-1 and other DNA binding sites. The different time-courses for individual immediate early gene products strongly suggest, that at different time-points after status epilepticus, different AP-1 complexes are effective. In vitro studies have shown that different AP-1 complexes possess different DNA binding affinities as well as different transcriptional regulatory effects. Our results suggest that these molecular mechanisms are also effective in vivo.
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PMID:Induction of immediate early gene encoded proteins in the rat hippocampus after bicuculline-induced seizures: differential expression of KROX-24, FOS and JUN proteins. 160 23

Regional cerebral blood flow (CBF) and regional cerebral glucose utilization (CGU) were studied by quantitative autoradiographic techniques in rats. Animals were treated either with a toxic dose of soman, an irreversible organophosphorus cholinesterase inhibitor, that produced convulsions or with saline as controls. An increased arterial blood pressure (mean increase = 41% of control) always preceded onset of convulsions. Convulsive activity was associated with an increase of plasma glucose concentration and marked increases over controls of CGU [average of all regions: control = 75 +/- 5 mumol.100 g-1.min-1, n = regions/animals (304/8); seizures = 451 +/- 20 mumol.100 g-1.min-1, n = 190/5] and CBF [average of all regions: control = 135 +/- 6 ml.100 g-1.min-1, n = 190/5; seizures = 619 +/- 29 ml.100 g-1.min-1, n = 190/5). Regional distribution of these effects revealed a greater proportional increase of CBF over CGU in cingulate, motor, and occipital cortex and caudate-putamen. In contrast, a lower proportional increase of CBF over CGU in CA3 region of hippocampus, dentate gyrus, medial thalamus, and substantia nigra was observed, implying the existence of a relative ischemia in these brain areas. These findings may be relevant to the pathogenesis of brain lesions associated with soman-induced convulsions.
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PMID:Cerebral blood flow and metabolism in soman-induced convulsions. 161 57

A small dose of tetanus toxin (2-5 ng; 10 mouse LD50) injected into the rat hippocampus produces a chronic epileptic syndrome in which epileptic discharges recur intermittently for 6-8 weeks. Hippocampal slices prepared during this period and maintained in vitro generate both evoked and spontaneous epileptic discharges. The present study used slices prepared 8-18 days after injection of tetanus toxin or vehicle solution into both hippocampi to test whether or not synaptic inhibition was selectively impaired in this experimental epilepsy. Intracellular recordings were made from CA3 pyramidal layer neurones within the tetanus toxin focus, which was identified by field potential recordings of synchronous bursts evoked by afferent stimulation. The intrinsic properties of these neurones did not differ from comparable cells in control-injected rats. All cells generated excitatory postsynaptic potentials (EPSPs) following stimulation of stratum radiatum in CA3. In control slices EPSPs were followed by a 'fast' inhibitory postsynaptic potential (IPSP), peaking at 25-30 ms, with a mean amplitude (+/- SEM) of -6.7 mV (+/- 0.66). In the epileptic slices these were absent, and the EPSP prolonged so that the potential at 30 ms was a depolarisation of +6.6 mV (+/- 2.75). The slow IPSP at 120 ms dropped to -0.27 mV (+/- 0.18) from -3.97 mV (+/- 1.43) (11 cells in each group). The loss of IPSPs cannot be attributed to a shift in reversal potentials in the toxin-injected group because no IPSPs were unmasked by current injection (n = 11). IPSPs also occurred spontaneously in the neurones in control slices, with a mean amplitude of -1.30 mV. Their frequency decreased by a factor of 13 in cells from the chronic focus induced by tetanus toxin (P less than 0.0001, analysis of variance), but their amplitude did not change significantly (mean of -1.22 mV). Spontaneous EPSPs were significantly more frequent and slightly smaller in the toxin-injected group (mean amplitudes 1.35 and 1.13 mV respectively). Together these studies support the hypothesis that the chronically recurring seizures induced by low doses of tetanus toxin can be attributed to a substantial, persistent and selective reduction of inhibitory neurotransmission in the hippocampus.
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PMID:Sustained and selective block of IPSPs in brain slices from rats made epileptic by intrahippocampal tetanus toxin. 161 77

In situ hybridization techniques were used to analyse the spatiotemporal pattern of brain-derived neurotrophic factor messenger RNA elevation associated with kainic acid-induced seizure activity in the rat. Pronounced increases in hippocampal brain-derived neurotrophic factor messenger RNA levels were observed as early as 30 min following the onset of behavioral seizures. The greatest increase (10-fold) occurred in the dentate granule cell layer, while pyramidal layers CA1, CA3, and CA4 exhibited increases of two- to six-fold. Peak elevation of brain-derived neurotrophic factor messenger RNA in CA1 hippocampal region was evident at 4 h in CA3, and in the dentate granule layer at 30 min postseizure. Elevations persisted in the dentate and hilar regions to four days, while the increases in CA1 and CA3 returned to control levels by 16 h following seizure. Significant increases in brain-derived neurotrophic factor messenger RNA were also observed in the superficial layers of cortex (II and III) and in the piriform cortex which reached peak elevations by 8 h. No detectable changes were observed in the dorsomedial thalamus. Although histologically defined pyramidal and granule cell layers displayed relatively uniform increases in brain-derived neurotrophic factor messenger RNA in response to kainate, a closer examination of the labeling patterns using emulsion autoradiography revealed discrete areas of high grain densities overlapping uniform, moderate hybridization densities in the dentate granule cell layer and CA3, suggesting that the capacity to upregulate brain-derived neurotrophic factor messenger RNA in these regions may differ among individual neurons. In conclusion, our studies revealed that brain-derived neurotrophic factor messenger RNA induction in response to systemic kainate administration differs in hippocampal and cortical areas, in magnitude, time of onset and duration. The observed temperospatial pattern does not correspond in a simple way to increases in metabolic or electrical activity associated with seizures or neuronal vulnerability coincident with the seizures.
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PMID:Regionally specific and rapid increases in brain-derived neurotrophic factor messenger RNA in the adult rat brain following seizures induced by systemic administration of kainic acid. 164 Nov 25

This study examined the interictal consequences of partial kindling of the ventral perforant path on attack and defensive behavior in the domestic cat. Partial kindling produced a lasting increase in defense response of cats to both rats and conspecific threat howls. In addition, there was a lasting suppression of approach-attack behaviors directed toward rats. The suppression of some components of approach-attack were shown to be independent of the increases in defensive response. The effects of partial kindling of the ventral perforant path on spread of seizure activity into the amygdala, and on the output of the amygdala to both the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST) were also examined. In addition, the effects of repeated hippocampal seizures on recurrent inhibition in the trisynaptic circuit (areas CA1 and CA3) were investigated. Growth of seizure activity in the amygdala and VMH as partial kindling progressed was essential for behavioral change. In addition, interictal long-term potentiation of potentials evoked in the VMH and in the BNST by pulsed stimulation of the amygdala followed partial kindling or afterdischarge threshold determination in the ventral perforant path. A lasting interictal increase in inhibition in area CA3 and a lasting interictal failure of inhibition in area CA1 of the ventral hippocampus also followed partial kindling. These changes in limbic physiology were related to the behavioral changes produced by partial kindling. The analysis revealed the importance of the amygdalo-VMH pathway in increased defensive response to rats. The amygdalo-BNST pathway is not important in mediating defensive response to prey, but it is implicated in suppression of some types of predatory aggression. Finally, changes in neural inhibition in the ventral hippocampus in areas CA1 and CA3 are associated with changes in both defensiveness and predatory aggression.
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PMID:Partial kindling of the ventral hippocampus: identification of changes in limbic physiology which accompany changes in feline aggression and defense. 164 39

Recordings from the CA3 region of hippocampal slices indicate a developmental change in the divalent cation sensitivity of the response elicited by N-methyl-D-aspartate (NMDA) application. In parallel experiments a developmental difference is demonstrated in the capacity of extracellular calcium to modulate electrographic seizure generation. Calcium modulation of the NMDA-elicited response may contribute to the pronounced capacity of immature hippocampus to generate electrographic seizures. Under these conditions activity dependent changes in extracellular calcium could have a greater influence on ion flow produced by activation of the NMDA receptor. The possibility that changes in the receptor isoform may occur during development would have widespread implications for normal cognitive functions and dysfunctions during brain maturation.
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PMID:Calcium modulation of the N-methyl-D-aspartate (NMDA) response and electrographic seizures in immature hippocampus. 164 82

We investigated whether modifications in noradrenergic neurotransmission occurred during the development of hippocampal kindling in rats. We measured the release of [3H]norepinephrine (NE) induced by field-electrical stimulation, NE-stimulation of inositol phosphates [( 3H]IP) accumulation in the presence of LiCl and isoproterenol-induced accumulation of cAMP in hippocampal slices taken from rats electrically kindled at stages 2 and 5 in the dorsal hippocampus. One week after the last of at least 3 consecutive stage 5 seizures or 48 h after the last stage 2 stimulation, 2 min electrical stimulation of stratum pyramidale CA1-CA3 or dentate gyrus (DG) slices from kindled and contralateral hippocampi induced frequency-dependent NE release (respectively 2, 4 and 8 times spontaneous release measured at 2, 5 and 10 Hz) which did not significantly differ from that observed in shams (implanted with electrodes but not stimulated). Basal release of NE from kindled and sham-treated rats did not differ either. Isoproterenol induced a dose-dependent increase above basal cAMP concentration ranging from 40% at 0.01 microM to 180% at 10 microM (P less than 0.01, Dunnett's test) which did not differ between stages 2 and 5 and sham-hippocampi. NE (1-1000 microM) induced a dose-dependent, prazosin-sensitive increase in [3H]IP accumulation in the hippocampal slices. A significantly higher increase was found at stages 2 (P less than 0.05, Tukey's test) and 5 (P less than 0.05 and P less than 0.01, Tukey's test) compared to shams at all doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in pre- and postsynaptic components of noradrenergic transmission in hippocampal kindling in rats. 166 Jul 53


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