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)

A transient brain ischemia of 30-min duration was induced by the four-vessel occlusion technique in normally fed and in 48-hr-fasted rats. Evaluation of brain damage 72 hr after ischemia showed that fasting reduced neuronal necrosis in the striatum, the neocortex, and the lateral part of the CA1 sector of hippocampus. Signs of status spongiosis in the pars reticulata of the substantia nigra were seen in 75% of fed rats and in only 19% of fasted rats. The protective effect was associated with reduction in mortality and in postischemic seizure incidence. The metabolic changes induced by fasting were evaluated before and during ischemia. After 30 min of four-vessel occlusion, fasted rats showed a marked decrease in brain lactate level (14.7 vs 22.5 mumol/g in fed rats; P less than 0.001). The decrease in brain lactate concentration might explain the beneficial effect of fasting by minimizing the neuropathological consequences of lactic acidosis. Several factors may account for lower lactate production during ischemia in fasted rats: hypoglycemia, reduction in preischemic stores of glucose and glycogen, or increased utilization of ketone bodies aiming at reducing the glycolytic rate.
 ...
PMID:Fasting prior to transient cerebral ischemia reduces delayed neuronal necrosis. 238 15

Hippocampal slices, from which the entorhinal cortex had been removed, were exposed to artificial cerebrospinal fluid containing no magnesium (0-Mg ACSF) to elicit interictal bursts (IIBs) and electrographic seizures (EGSs). In 0-Mg ACSF, IIBs and EGSs occurred in both area CA1 and area CA3. The IIBs in CA3 led the IIBs in CA1 by several milliseconds. The epileptiform bursts occurring during the EGSs seemed to have the opposite relationship, with bursts in CA1 leading those in CA3 by several milliseconds. When the connections between CA1 and CA2-3 were cut, the IIBs ceased in CA1 and continued in CA3. To further characterize the local differences in epileptiform activity, totally separate minislices of area CA1 and area CA2-3 were prepared. In the CA2-3 minislices, a few EGSs occurred and thereafter only persistent IIBs prevailed. Conversely, in the CA1 minislices, many spontaneous EGSs occurred for long periods of time and no IIBs were seen. Periodic stimulation of the CA1 minislices triggered IIBs that suppressed the recurrent EGSs. In the hippocampal slice exposed to low magnesium, IIBs originate in CA2-3 and are propagated to CA1, where they can have a suppressant effect on EGSs. Furthermore, unlike IIBs, the bursts making up the EGSs seem to start in CA1 and invade CA2-3.
 ...
PMID:Hippocampal epileptiform activity induced by magnesium-free medium: differences between areas CA1 and CA2-3. 238 88

Recently, a theoretical scheme offered mechanisms by which phenytoin exerts its antiepileptic effects. Two predictions arising from this proposal are that phenytoin would suppress alterations in the potency of excitatory neurotransmission engendered by repetitive neural activation and that this effect would be augmented by displacing the extracellular concentration of K+ ([K+]0) away from its normal resting level. In the present study, we tested these predictions by examining the effects of phenytoin on short- and long-term functional plasticity in vitro in the hippocampus. Extracellular field potentials were recorded in the CA1 region of the rat hippocampal slice in response to stimulation of the Schaeffer collaterals. Phenytoin (20 micrograms/ml) did not affect baseline excitatory neurotransmission as measured by input-output curves (population spike amplitude versus stimulus intensity) obtained at low stimulus rates. The drug also had no effect on either frequency potentiation (2.5 Hz) or long-term potentiation (50 Hz, 500 msec; or 400 Hz, 20 msec). When [K+]0 was raised to levels seen during seizures, the drug still did not alter frequency potentiation or long-term potentiation induced by either type of stimulus train. Phenytoin also had no effect on either stimulus-locked or spontaneous epileptiform bursts that appear in conjunction with elevated [K+]0 or on stimulus-locked bursts that appear in the presence of 0.75 mM extracellular calcium. These results, showing that certain forms of functional synaptic plasticity are not affected by phenytoin, suggest a means by which phenytoin could exert its antiepileptic action without interfering with normal brain function.
 ...
PMID:Phenytoin does not block hippocampal long-term potentiation or frequency potentiation. 245 69

A paired-pulse stimulus protocol was used to measure angular bundle to dentate gyrus paired-pulse inhibition in rats before and after the occurrence of 36 or 72 seizures elicited from the contralateral CA3 region. The seizures showed progressive lengthening. There was a moderate increase in paired-pulse depression 1 h after 36 seizures and a further increase after 72 seizures. These data demonstrate that the same experimental protocol which produced a decrease in paired-pulse inhibition in the CA1 region caused the opposite effect in the dentate gyrus.
 ...
PMID:Repetitive seizures cause an increase in paired-pulse inhibition in the dentate gyrus. 248 90

The present study was designed to determine whether inhibitory neurons in human epileptic hippocampus are reduced in number, which could reduce inhibition on principal cells and thereby be a basis for seizure susceptibility. We studied the distribution of GABA neurons and puncta by using glutamate decarboxylase (GAD) immunocytochemistry (ICC) together with Nissl stains. Using quantitative comparisons of GAD-immunoreactive (GAD-IR) neurons and puncta in human epileptic hippocampus and in the normal monkey hippocampus, we found that GAD-IR neurons and puncta are relatively unaffected by the hippocampal sclerosis typical of hippocampal epilepsy where 50-90% of principal (non-GAD-IR) cells are lost. GAD-IR neurons and puncta were not significantly decreased compared with normal monkey. In 6 patients, prior in vivo electrophysiology demonstrated that the anterior hippocampus generated all seizures. The anterior and posterior hippocampus were processed simultaneously, and the counts of hippocampal GAD-IR neurons were numerically greater in anterior than in the posterior hippocampus, where no seizures were initiated. These results indicate that GABA neurons are intact in sclerotic and epileptogenic hippocampus. Computerized image analysis of puncta densities in fascia dentata, Ammon's horn, and subicular complex in epileptic hippocampi (n = 7) were not different from puncta densities in the same regions in normal monkey (n = 2). Hence, despite the significant loss of principal cells (50-90% loss) GABA terminals (GAD-IR puncta) were normal, which suggests GABA hyperinnervation of the remnant pyramidal cells and/or dendrites in human epileptic hippocampus. The apparent increase in puncta ranged from 2 (fascia dentata) to 3.3 (CA1) times normal puncta densities. These findings would suggest increased inhibition and less excitability; however, those regions were epileptogenic. We suggest that GABA terminal sprouting or hyperinnervation of the few remnant projection cells may serve to synchronize their membrane potentials so that subsequent excitatory inputs will trigger a larger population of neurons for seizure onset in the hippocampus and propagation out to undamaged regions of subiculum and neocortex.
 ...
PMID:Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus. 250 60

1. Minute doses of tetanus toxin were injected into the hippocampi of rats, under pentobarbitone anesthesia, to induce a chronic experimental epilepsy. The effects of this treatment were studied in vitro in hippocampal slices prepared 1-60 days after injection. 2. Epileptic activity was preserved in these slices in vitro, closely resembling that seen in vivo. Epileptiform afterdischarges were evoked by stimulation after survival times of greater than or equal to 3 days from injection. Spontaneous synchronous epileptic discharges were recorded from 7 days after injection. Both kinds of epileptiform activity were found with survival times up to 36 days but not beyond 44 days. This time course resembles the waxing and waning of the epileptic syndrome in vivo. 3. Two distinct types of spontaneous burst were seen. The first was a simple burst lasting 100-300 ms, reminiscent of the "interictal spike" of the clinical electroencephalogram. The second was much more prolonged, lasting several seconds. It consisted of a simple burst followed by a series of discrete afterbursts at 3-6/s and resembled the early stages of an epileptic seizure. Both types of burst were associated with slow field potentials that were positive at the cell-body layer. 4. Both the interictal and the seizure-like spontaneous epileptic discharges originated in the CA3b/c pyramidal cell region and propagated at 0.1-0.25 m/s along the cell layer toward the CA1 region. They occurred at very variable intervals, ranging from 20 s to 30 min. 5. Spontaneous epileptic bursts occurred in media containing 3 mM [K+]o to 5 mM in one-third of experiments during the period 1-4 wk after injection. Spontaneous bursts could be induced by increasing [K+]o to 5 mM in two-thirds of the remaining slices, which initially had produced evoked afterdischarges. 6. Intracellular recordings revealed that spontaneous field bursts were invariably associated with paroxysmal depolarization shifts (PDSs) and bursts of action potentials, suggesting that almost all the pyramidal cells in the region were recruited into the epileptic discharges. In some cells, smaller abnormal depolarizations were also seen; they were clearly larger than the spontaneous synaptic potentials but were not associated with field potentials. They may have been due to a more limited recruitment of pyramidal cells into partially synchronous bursts. 7. The tetanus toxin experimental epileptic syndrome differs from chronic models described previously in retaining in the hippocampal slice in vitro much of the spontaneous epileptic activity seen in vivo in the freely moving chronically epileptic rat.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Chronic epileptic foci in vitro in hippocampal slices from rats with the tetanus toxin epileptic syndrome. 250 91

Electrically evoked hippocampal afterdischarges are used as a model of partial epileptic seizures with a complex symptomatology and for testing anticonvulsants and toxic substances. Stimulating electrodes were implanted in the dorsal hippocampus of 16 laboratory rats and when the animals had recovered they were stimulated (15-s series, 8 Hz, pulse length 1 ms) with a voltage double the threshold value for a tissue response. The following features of the evoked afterdischarge were evaluated: the duration of the first phase of the afterdischarge, the duration of the non-active interphase, the duration of the second phase and the number of "wet dog shakes" (a constant accompaniment of hippocampal afterdischarges). Localization of the electrodes in the CA1 (n = 7) and CA3 (n = 7) region of the hippocampus made no difference to these parameters and in both cases the measured and evaluated data were the same. The afterdischarges were always accompanied by a marked orientation reaction. The study showed that when using macroelectrodes to stimulate the dorsal hippocampus, their localization in the CA1/CA3 is not of critical importance.
 ...
PMID:Hippocampal afterdischarges and localization of the stimulating electrodes. 253 30

The effects of a selective kappa-agonist, U-50,488H, on systemic kainic acid-induced behavioral and histological changes were studied in rats. U-50,488H inhibited kainic acid-induced wet dog shakes in a naloxone reversible manner; however, U-50,488H did not protect rats against kainic acid-evoked behavioral seizures. As revealed by histological analysis, kainic acid caused edema and severe neuronal damage in several brain regions, notably in CA1 but also in the CA3 fields of both hippocampi. Pretreatment of rats with U-50,488H markedly protected hippocampal neurons, especially those in CA1, against kainic acid-induced neurotoxicity. Naloxone by itself had little effect on kainic acid-induced seizures or hippocampal neuron loss. Naloxone plus U-50,488H resulted in less severe seizures and, consequently, less hippocampal cell loss than after kainic acid alone. These data indicate that U-50,488H can markedly attenuate the neurotoxic and behavioral consequences of systemic kainic acid administration. However, the mechanism of these effects requires further study with more specific opioid antagonists.
 ...
PMID:The interaction between kappa-opioid agonist, U-50, 488H, and kainic acid: behavioral and histological assessments. 253 86

The novel compound 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) was evaluated for activity in a variety of tests associated with receptors for excitatory amino acids. NPC 12626 failed to inhibit the specific binding of RS-[3H] amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid or [3H] kainic acid to brain membranes in vitro but displaced both agonist and antagonist binding to N-methyl-D-aspartic acid (NMDA) receptors. Like cis-(+/-)-3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid, NPC 12626 competitively blocked NMDA-induced enhancement of [3H]-1-thienylcyclohexyl)piperidine binding. In the voltage-clamped frog oocyte expression system, NPC 12626 was a competitive inhibitor of NMDA-evoked inward current with a pA2 of 6.24. After both i.c.v. or i.p. administration, NPC 12626 was a potent anticonvulsant in the pentylenetetrazol, maximal electroshock and NMDA seizure models. Furthermore, low doses (25 mg/kg) of NPC 12626 given i.v. were effective in preventing damage to the CA1 region of hippocampus in the gerbil model of global ischemia. Unlike the noncompetitive NMDA antagonist, phencyclidine, but like cis-(+/-)-3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid and pentobarbital, NPC 12626 only partially substituted for phencyclidine in a drug discrimination study. The results of the current study indicate that NPC 12626 is a novel, systemically active and competitive NMDA receptor antagonist.
 ...
PMID:Pharmacological profile of NPC 12626, a novel, competitive N-methyl-D-aspartate receptor antagonist. 254 56

The specific binding of L-[3H]glutamate to N-methyl-D-aspartate (NMDA) receptors in brain regions of kindled rats was visualized autoradiographically and quantitated. When assayed 28 days after the last evoked seizure, NMDA receptor binding had declined by 7-11% in stratum radiatum of the dorsal hippocampal area CA1, in both deep and superficial layers of the motor cortex and in layers I-IV of the somatosensory cortex. No significant changes were detected in any other brain region nor in any region examined 1 day after the last evoked seizure. These findings suggest that the enhanced activation of NMDA receptors in kindled rats cannot be explained by an increased expression of these receptors. Rather, kindling leads to a regionally-selective down regulation of NMDA receptor binding.
 ...
PMID:N-methyl-D-aspartate receptor autoradiography in rat brain after angular bundle kindling. 256 43


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