Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the anticonvulsant and adverse behavioral effects of lamotrigine (LTG), a novel antiepileptic drug (AED), as well as other conventional AEDs on kindled seizures in rats. We also applied an anticonvulsive dose of LTG in vivo to rats in which the hippocampus had been subjected to long-term potentiation (LTP). LTG potently attenuated limbic-kindled seizures in a dose-dependent fashion, at doses at which animals showed no adverse behavioral effects. LTG was effective in preventing kindled seizures for up to 24 h after a single i.p. administration. The anticonvulsant effects of LTG were reversed when the stimulus current was raised to two or three times the generalized seizure-triggering threshold. Among the AEDs examined, valproate and LTG were the only drugs that engendered a potent anticonvulsant effect without concomitant adverse behavioral effects. Although all of the other AEDs exhibited anticonvulsant effects with various potencies, they produced adverse effects such as sedation or motor ataxia. Furthermore, an anticonvulsant dose of LTG did not affect either the induction or maintenance of tetanus-induced LTP in the hippocampus. These results indicate that LTG potently suppresses limbic-kindled seizures by raising the seizure triggering-threshold in the kindling focus at doses that do not affect LTP in the hippocampus.
 ...
PMID:Effects of lamotrigine and conventional antiepileptic drugs on amygdala- and hippocampal-kindled seizures in rats. 971 1

To explore the anatomical substrates for network hyperexcitability in adult rats that become chronically epileptic after recurrent seizures in infancy, the dendritic and axonal arbors of biocytin-filled hippocampal pyramidal cells were reconstructed. On postnatal day 10, tetanus toxin was unilaterally injected into the hippocampus and produced brief but recurrent seizures for 1 week. Later, hippocampal slices taken from these rats exhibited synchronized network bursts in area CA3C. Both the apical and basilar dendritic arbors of CA3C pyramidal cells were markedly abnormal in these epileptic rats. There was a considerable reduction in the density of dendrite spines, although the extent of this loss could vary among dendritic segments. Spine density on terminal segments of the basilar and apical dendrites was reduced on average by 35 and 20%, respectively. In addition, the diameters of these same dendritic segments were markedly reduced. Dendritic spine loss has previously been suggested to indicate a partial deafferentation of epileptic neurons, but this interpretation is difficult to reconcile with the critical role recurrent excitatory synaptic transmission plays in the generation of synchronized network burst. In this study, axonal arbors of CA3C pyramidal cells exhibited normal branching patterns, branching complexity, and varicosity density. This suggests that if deafferentation occurs, synapses other than recurrent excitatory ones are lost. The morphological abnormalities reported here would be expected to significantly alter electrical signaling within dendrites that may contribute importantly to seizures and other behavioral sequelae of early-onset epilepsy.
 ...
PMID:Spine loss and other persistent alterations of hippocampal pyramidal cell dendrites in a model of early-onset epilepsy. 976 79

Studies were conducted to characterize a chronic epileptic condition that follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infancy. Wistar rat pups received a single injection of tetanus toxin in the right CA3 region on postnatal day 10. Animals were monitored for epileptiform activity by video electroencephalographic or visual observation during the following three to five days. Repeat evaluation six months later demonstrated interictal discharges in 79% (11 of 14) and electrographic seizures in 42% (six of 14) of adult rats with tetanus toxin-induced seizures in infancy. Five of the animals had interictal activity which occurred focally in either the left (n = 2) or right (n = 3) hippocampus. One animal had focal interictal activity independently in these regions and in the left and right cortical regions. The remaining five animals had interictal activity in the hippocampus and synchronously in the ipsilateral cortex or the contralateral hippocampus. Electrographic seizures were focal (nine of 14) or bilateral (five of 14) in onset. The behaviors that accompanied these seizures were quite variable. Clonic face and forelimb movements were observed in some animals. However, a significant portion of rats had electrographic seizures with no associated behavioral change. Timm staining was performed on hippocampal sections from experimental and control animals. There was a significantly greater Timm score (aberrant Timm granules) in the inner molecular layer of the dentate gyrus in tetanus toxin-treated rats than in control rats. Our findings suggest that intrahippocampal tetanus toxin injection in infant rats results in a chronic focal epilepsy that persists for at least six months and is associated with aberrant mossy fiber sprouting in the dentate gyrus. The model described here contributes significantly to the evidence for chronic effects of recurrent seizures in early life, and provides a model for investigation of the molecular and cellular events that contribute to the development of chronic epilepsy.
 ...
PMID:A chronic focal epilepsy with mossy fiber sprouting follows recurrent seizures induced by intrahippocampal tetanus toxin injection in infant rats. 1039 31

Three piscivorous Conus species, C. ermineus, C. consor and C. catus were acclimatized in aquaria. The study of their strategy to capture the prey and details of their radula's morphology revealed that all of them used a 'hook and line' strategy which consists of immobilizing the prey rapidly before engulfing it. The venoms from these piscivorous species clearly elicit, when injected into fish, an excitotoxic shock characterized by a sudden tetanus of the prey. In mammals, the venoms induce both flaccid paralysis via i.p. injection and seizures via i.c.v. injection. Intracellular recordings from frog nerve-muscle preparations revealed that the venoms from these Conus species first caused spontaneous synaptic potentials which in turn triggered muscle action potentials. Such spontaneous activity is due to an increased nerve terminal excitability. In addition, the venoms suppressed neuromuscular transmission probably by blocking postsynaptic nicotinic acetylcholine receptors. No direct effect of these Conus venoms was observed on the membrane of skeletal muscle fibres. In conclusion, C. ermineus, C. consor and C. catus, which have not securely tethered their prey used a mixture of toxins which target both pre-and postsynaptic elements of the neuromuscular junction and which produce rapid immobilization of their prey.
 ...
PMID:The strategy used by some piscivorous cone snails to capture their prey: the effects of their venoms on vertebrates and on isolated neuromuscular preparations. 1048 46

Both clinical and experimental studies suggest that the immature nervous system is unusually susceptible to seizures during critical periods in postnatal life. A late onset of gamma-aminobutyric acid (GABA)-mediated synaptic inhibition could conceivably play a contributing role in this phenomenon. Numerous studies have shown that neural systems that use GABA in the neonatal brain are different than those of adulthood. GABA is an excitatory neurotransmitter that likely plays a neurotrophic role in neuronal differentiation. Other reports suggest that unique, possibly transient, GABAergic interneuron populations exist in the embryonic and neonatal nervous system. At these early times in development, the immature nervous system is remarkably resistant to seizure generation. However, as the hippocampus and neocortex enter the critical period of enhanced seizure susceptibility, inhibitory GABA systems mature rapidly. At this time, blockade of GABA type A (GABAA) receptors produce unusually severe seizure discharges. In hippocampus, concurrent exuberant outgrowth of recurrent excitatory axon collaterals and synapses appear to play a role in the generation of these seizures. As the hippocampus matures, these axons are morphologically remodeled and nearly 50% of branches within arbors are pruned. This pruning of axon branches corresponds in time with the decrease in seizure susceptibility that characterizes adulthood. Developmental remodeling of neuronal connectivity is a common feature of most areas of the central nervous system. Results from an audiogenic seizure model of early onset epilepsy suggest that prevention of axon arbor remodeling by transient sensory deprivation can lead to a permanent overinnervation of target nuclei and chronic seizure susceptibility. Early life seizures may have a similar effect. Recent results in one model have shown that repeated seizures induced by intrahippocampal injections of tetanus toxin during a critical period results in a chronic epilepsy. Future studies should attempt to determine if the synchronized discharging of early-life seizures prevents the remodeling of neuronal connectivity that normally takes place during postnatal development and results in an overinnervated and chronically hyperexcitable hippocampus.
 ...
PMID:Developmental neuroplasticity: roles in early life seizures and chronic epilepsy. 1051 15

Video monitoring studies were undertaken to determine if the anticonvulsant, carbamazepine (CBZ), could prevent seizures in infant rats that had been intrahippocampally injected with tetanus toxin (TNTX). In control rats, seizure frequency peaked 5-6 days after injection and rapidly declined by postinjection day 9. Twice-daily CBZ treatments dramatically suppressed behavioral seizures for 7 days. However, despite increasing the dosage of CBZ, rats experienced more behavioral seizures during the second week after TNTX injection. Paradoxically, tetanus-toxin-injected control rats had very few seizures at this time. Results not only suggest that this TNTX model may be useful in screening drugs for treating intractable focal epilepsy of infancy but also provide some insight into the processes that may contribute to the rapid decline in behavioral seizure frequency that occurs during the acute phase of epileptogenesis in this model.
 ...
PMID:Insights into the tetanus toxin model of early-onset epilepsy from long-term video monitoring during anticonvulsant therapy. 1061 23

Unilateral intrahippocampal injection of tetanus toxin results in a chronic syndrome of intermittent epileptic seizures. During some of these seizures, rats develop a stereotypic, pathological motor behavior that indicates secondary generalization of epileptic activity. We report that secondary generalization was preceded by a 9-16 Hz oscillation of field potentials which was synchronized between the right and left dorsal hippocampi. The oscillation was associated with increased synchrony of population spike firing in right and left CA1 subregions which form the major output of the hippocampi. Cutting the ventral commissure abolished synchrony across the hippocampi and reduced the probability that the 9-16 Hz activity would be followed by secondary generalization. We concluded that a bilaterally synchronous 9-16 Hz hippocampal oscillation played a role in the secondary generalization of focal seizures in this chronic model of limbic epilepsy.
 ...
PMID:9-16 Hz oscillation precedes secondary generalization of seizures in the rat tetanus toxin model of epilepsy. 1075 30

The present study examined the effects of prenatal morphine exposure on NMDA-dependent seizure susceptibility in the entorhinal cortex (EC), and on activity-dependent synaptic plasticity at Schaffer collateral and perforant path synapses in the hippocampus. During perfusion with Mg(2+)-free ACSF, an enhancement of epileptiform discharges was found in the EC of slices from prenatally morphine-exposed male rats. A submaximal tetanic stimulation (2x50 Hz/1 s) in control slices elicited LTP at the Schaffer collateral-CA1 synapses, but neither LTP nor LTD was evoked at the perforant path-DG synapses. In slices from prenatally morphine-exposed adult male rats, long-term potentiation of synaptic transmission was not observed at Schaffer collateral-CA1 synapses, while the submaximal tetanus now elicited frank LTD of synaptic EPSPs at perforant path synapses. These data suggest that prenatal morphine exposure enhances the susceptibility of entorhinal cortex to the induction of epileptiform activity, but shifts long-term plasticity of hippocampal synapses in favor of LTD.
 ...
PMID:Prenatal morphine exposure enhances seizure susceptibility but suppresses long-term potentiation in the limbic system of adult male rats. 1086 73

Pertussis infection is associated with significant morbidity in younger children (<4 years), which can include pneumonia, seizures and encephalopathy. Around one in 250 cases of pertussis in infants under the age of 6 months lead to death or severe brain damage. In the United Kingdom the control of pertussis infection has been based on a three-dose schedule of combined diphtheria, tetanus, whole-cell pertussis vaccine (DTPw) during the first 4 months of life. Coverage rates for primary vaccination are currently at high levels of over 90 per cent and infection rates are relatively low (approximately 1.2 per 100,000). However, there are concerns over the potential under-reporting of pertussis and clear shifts in the age pattern of notified cases are evident, with surveillance data suggesting a possible upward trend in the absolute numbers of infections in those at most risk (i.e. infants <3 months old). The addition of childhood booster dose(s) of pertussis vaccine to the standard schedule has potential clinical benefits and may be cost-effective. Selective adult booster immunization may also have a role to play in controlling the circulation of pertussis.
 ...
PMID:Do we need to boost pertussis immunization within the existing UK vaccination schedule? 1107 9

The question we attempted to address in this chapter is: Do brief but recurrent seizures in early life alter the ontogeny of hippocampal networks in ways that produce epileptic circuits? Results from the tetanus toxin model suggest that this is likely the case. Following seizures in Postnatal Weeks 2 and 3, most adult rats have a focal epilepsy that arises from hippocampus. Recordings from hippocampal slices support this conclusion since they demonstrated the occurrence of spontaneous network discharges in normal artificial cerebrospinal fluid. Moreover, when GABA-A receptor-mediated synaptic transmission was suppressed, slices from adult epileptic rats produced prolonged electrographic seizures which are never observed in control rats. This suggests that hyperexcitable recurrent excitatory networks contribute to hippocampal seizures in this model. In light of this, anatomical results from biocytin-filled neurons were surprising. Results suggest that recurrent axon arbors neither sprout additional branches as a result of seizure activity nor maintain their exuberant branching patterns of early life. Thus, excessive connectivity cannot explain seizure generation. Axon arbors either remodel in normal ways or prune additional collaterals as a result of ongoing epileptiform discharging. At the same time that axon arbors remodel, the dendrites of these cells have decreased dendritic spine density, suggesting a partial deafferentation. While a complete understanding of the origins of spine loss requires further investigation, we hypothesize that this loss is a product of a partial deafferentation that occurs due to excessive and abnormal selection of synaptic connections. Network-induced heterosynaptic LTD of noncoincidentally active afferants may be one mechanism that leads to a loss of synapses. Moreover, competition among and selection between individual recurrent excitatory synapses may contribute to spine loss as well. The "winners" of this competition, the most potent and effective early-formed recurrent excitatory synapses, are likely key contributors to seizure generation in this model and possibly in humans with early-onset temporal lobe epilepsy.
 ...
PMID:Neuronal activity and the establishment of normal and epileptic circuits during brain development. 1113 Sep 18


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