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)

These studies were conducted to determine whether amygdaloid kindling results in the long-term alteration of NMDA receptors which could explain the persistent reduction in seizure threshold seen in this phenomenon. NMDA-induced [3H]norepinephrine (NE) release, NMDA-sensitive L-[3H]glutamate binding, and NMDA and glycine-enhanced [3H]TCP binding were measured in brain tissue from kindled rats and nonstimulated control rats 3 to 6 weeks after the last seizure. There was no difference in the ability of NMDA to induce [3H]NE release from kindled or control slices of amygdala or hippocampus. There was also no difference in the ability of phencyclidine (PCP) or Mg2+ to inhibit [3H]NE release induced by 100 microM NMDA. Equilibrium saturation experiments of NMDA-sensitive L-[3H]glutamate binding revealed no differences in KD or Bmax values between control and kindled cortex, amygdala, and hippocampus. The Ki values for NMDA displacement of L-[3H]glutamate binding also did not differ in kindled tissue. NMDA-enhanced [3H]TCP binding was similar in cortex, amygdala, and hippocampus of kindled and control tissues. Finally, glycine-enhanced [3H]TCP binding was not different in control or kindled tissues. These studies suggest that the NMDA recognition site and the modulation of the NMDA receptor/ion channel complex by magnesium, PCP, and glycine are not altered several weeks after the last seizure. Even though NMDA-mediated electrophysiological responses are reportedly enhanced in kindled tissue at that time, the mechanism(s) underlying the enhancement remains to be determined.
 ...
PMID:Effects of amygdaloid kindling on NMDA receptor function and regulation. 257 16

Total, Mg2+-, Na+,K+-, and Ca2+-ATPase activities were studied in fresh brain membrane preparations from adult epileptic (El) mice and nonepileptic C57BL/6J (B6) mice. The El mice have an inherited type of temporal lobe epilepsy. No significant differences were observed between the El and B6 mice for any of the ATPase activities in the hippocampus, brain stem, or cerebellum. These findings indicate that seizure susceptibility in El mice is not associated with differences in the activities of these cationic ATPases and that seizure susceptibility in El mice and audiogenic DBA/2 mice may involve different biochemical mechanisms.
 ...
PMID:Brain cationic ATPase activities in epileptic (El) mice. 283 Jan 30

Decreases in extracellular sodium concentration [( Na+]o) and associated slow negative field potentials (fp's) were monitored with double barreled sodium sensitive/reference microelectrodes in area CA1 of rat hippocampal slices during iontophoretic application of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and quisqualate (quis). The effects of lowering [Ca2+]o on these signals were compared to those of lowering [Mg2+]o. Both NMDA- and quis-induced decreases in [Na+]o of up to 60 mM and in the fp's of up to 8 mV. Decreasing [Mg2+]o enhanced NMDA-induced signals, whereas quis-induced signals were unaffected. Lowering [Ca2+]o also enhanced NMDA signals, although somewhat less than lowering [Mg2+]o. This effect was still present, even when voltage dependent Na+ currents were blocked by 10(-7) tetrodotoxin. Interestingly, quis-induced signals could be enhanced in a low Ca2+ medium as well, but only when high quis concentrations were used. The results suggest that, during the sorts of large decreases of [Ca2+]o observed during seizure activity, activation of NMDA receptors is facilitated.
 ...
PMID:Differences in magnesium and calcium effects on N-methyl-D-aspartate- and quisqualate-induced decreases in extracellular sodium concentration in rat hippocampal slices. 284 78

It is widely held that a glutamate-like toxin that resembles N-methyl-D-aspartate may be responsible for the death of nerve cells seen after severe neurological insults including stroke, seizures, and degenerative disorders, such as Huntington disease, Alzheimer disease, and the amyotrophic lateral sclerosis-parkinsonism-dementia complex found on Guam. One puzzling fact about these maladies is the differential vulnerability of specific groups of neurons peculiar to each condition. We report here that an identified population of central neurons, rat retinal ganglion cells, are resistant to the neurotoxic effects of millimolar concentrations of glutamate under otherwise normal culture conditions. Patch-clamp experiments show that this resistance is associated with a very small ionic current response to N-methyl-D-aspartate. Varying the ionic milieu by increasing the extracellular Ca2+ concentration, however, results in a striking increase in glutamate-induced cell death in this population. Under these conditions, Mg2+ or the amino acid antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo-(alpha,gamma)-cyclohepten-5 ,10-imine maleate], blockers of N-methyl-D-aspartate receptor-coupled ion channels, completely abrogate the lethal effects of glutamate. These findings strongly suggest that Ca2+ entry through N-methyl-D-aspartate-activated channels is responsible for this type of neuronal death and suggest strategies that may be clinically useful in the treatment of various neurological disorders.
 ...
PMID:Central mammalian neurons normally resistant to glutamate toxicity are made sensitive by elevated extracellular Ca2+: toxicity is blocked by the N-methyl-D-aspartate antagonist MK-801. 290 Nov 1

Audiogenic seizure (AGS)-susceptible DBA/2 (D2) mice have a significant reduction in brain Ca2+-ATPase activity compared to AGS-resistant C57BL/6 (B6) mice. This reduction is inherited together with AGS susceptibility in B6 X D2 recombinant inbred strains. The Ca2+-ATPase reduction occurs in microsomes and synaptosomes, but not in mitochondria. This enzyme activity is measured at a high Ca2+ concentration (2 mM) with no added Mg2+ or EGTA. We further studied this Ca2+-ATPase activity and a Mg2+-dependent (Ca2+ + Mg2+)-ATPase activity in synaptic plasma membranes (SPM) from the B6 and D2 strains. Using EGTA or CDTA to adjust free Ca2+ concentrations, we measured Ca2+-ATPase activities at Ca2+ concentrations from 0.8 microM to 436 microM. The Ca2+-ATPase activity is consistently lower in the D2 than in the B6 SPM over all Ca2+ concentrations. The basal Mg2+-ATPase activity measured at 2 mM MgCl2, is also lower in SPM of D2 than B6 mice. Calcium stimulates the basal Mg2+-ATPase activity to the same extent in the SPM of the B6 and the D2 mice. Maximum stimulation in both strains occurs at 150 microM added CaCl2 (buffered with 100 microM EGTA). Higher Ca2+ concentrations inhibit this ATPase activity similarly in both strains. The EGTA-EDTA washing of SPM significantly reduces by 50% of the (Ca2+ + Mg2+)-ATPase activities of both strains, whereas calmodulin treatment restored these activities. Neither of these treatments, however, has any noticeable effects on the Ca2+-ATPase activities of the strains.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Calcium ATPase activities in synaptic plasma membranes of seizure-prone mice. 293 83

Primary hypomagnesemia with secondary hypocalcemia (PHSH) is a rare type of hypocalcemic disorder which occurs in early infancy and is clinically characterized by recurrent tetany and/or convulsion. In this paper, a male infant with PHSH who had frequent seizures at the age of 9 days is described. Besides PHSH, several illnesses in infancy are manifested by hypomagnesemia and hypocalcemia, i.e. transient neonatal hypomagnesemic hypocalcemia, congenital renal or hepatic insufficiencies, magnesium-losing nephropathy, combined impairments of intestinal absorption and renal reabsorption of magnesium. PHSH is to be differentiated from these illnesses by the demonstration of a combination of the following findings; hypocalcemia refractory to calcium but responsive to magnesium, continuous requirement for magnesium supplementation to maintain normocalcemia, lack of hypermagnesiuria and/or impaired intestinal absorption of magnesium. Twenty cases from the literature were found to exhibit these characteristics. The clinical, biochemical, and endocrine features of PHSH are summarized on the basis of a review of the data of these and the present case. No associated illness was known in the afflicted infants or mothers. Both male and female infants were afflicted at a male to female ratio of 15:6. Some siblings were afflicted but none of the parents or relatives. The onset of tetany and/or convulsion was between the 9th day and 4th month, which is later than that of other neonatal hypocalcemic illnesses. Hypocalcemia was more pronounced than other infantile hypocalcemic illnesses. The role of the parathyroid hormone in the pathogenesis of hypocalcemia has been studied in several studies but no unifying concepts have yet been established.
Magnesium 1985
PMID:Primary hypomagnesemia with secondary hypocalcemia. Report of a case and review of the world literature. 299 35

Seizure-like discharges were observed in slices of human epileptogenic neocortex maintained in vitro when [Mg2+]o was lowered near to zero. This type of epileptiform activity: (1) could occur spontaneously or following extracellular focal stimuli; (2) resembled the electrographic pattern associated with tonic-clonic seizures; (3) was accompanied by increases in [K+]o (maximally 6.2 mM from a baseline of 3.25 mM) and decreases in [Ca2+]o (maximally 0.23 mM from a baseline of 1.8 mM). Application of the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, DL-2-amino-5-phosphonovalerate, suppressed in a reversible manner both spontaneous and stimulus-induced seizure-like discharges, suggesting that NMDA-activated conductances are important for the genesis of prolonged epileptiform discharges generated by human epileptogenic neocortical slices.
 ...
PMID:Seizure-like discharges induced by lowering [Mg2+]o in the human epileptogenic neocortex maintained in vitro. 304 Jan 83

Fourty-nine patients were examined with epileptic seizures and values of serum and erythrocyte magnesium (sMg, RBC Mg) and serum zinc (sZn) were determined. Chronic deficiency in RBC Mg and sZn were confirmed. The percentage of patients with decreased RBC Mg increased with the time of antiepileptic treatment; significant lowering occurs after 5 years of treatment for RBC Mg and within 5 years for sZn. Various antiepileptics and their combinations have different effects on the degree of the lowering. The therapy of magnesium lactate produces significantly higher RBC Mg and sZn. The clinical, electroencephalographical and biochemical findings are improved.
Magnesium 1987
PMID:Metabolism of magnesium and zinc in patients treated with antiepileptic drugs and with magnesium lactate. 312 21

Recently, we have reported that the exposure of hippocampal slices in vitro to artificial cerebrospinal fluid (ACSF) containing no added magnesium results in ictal-like (ictaform) activity in area CA3 of the hippocampal formation. Other reports describe such activity in slices of entorhinal cortex (EC) under similar conditions. Because of the close interrelationship between the entorhinal area and the hippocampal formation, we have begun to study, in vitro, brain slices which contain both the entorhinal cortex and the hippocampal formation. In these slices, we have found that, in the magnesium-free (0-Mg2+) model, there is good electrical communication between area CA3 and the EC. Simultaneous recordings of the activity in the EC and CA3 showed that, when the circuitry linking the two areas was intact, the EC tended to initiate the ictaform activity and lead CA3. However, late in the event, CA3 could lead EC. Furthermore, interictal-like spontaneous bursting in CA3 led to a disorganized pattern of ictaform activity in EC. Finally, when the EC was separated from the hippocampal formation, both areas were capable of ictaform activity which was temporally unrelated. This model provides the opportunity to explore the relationship between two epileptogenic areas in vitro, and to compare and contrast the morphology of the ictaform activity present in both structures. As such, it may prove valuable in both pharmacological and physiological studies of seizure disorders.
 ...
PMID:Seizure activity in vitro: a dual focus model. 319 98

A light and electron microscopic study of Mg-deficient weanling rats showed structural changes of the lungs associated with the audiogenic seizure-shock episode, and with sudden, spontaneous death or spontaneous recovery after the shock episode. Pathogen-free weanling males were fed a Mg-deficient (Mg-0) or Mg-sufficient (Mg-100) diet and were raised in a gnotobiotic environment. Mg-100 rats (n = 16), unstressed or stressed with noise or strychnine, showed normal lungs. Mg-0 rats (n = 20) experienced audiogenic seizure-shock, followed by hyperventilation with tonic-clonic hyperextension of the back and extremities. The lungs of Mg-0 rats sacrificed during shock showed marked hemorrhage, including petechiae; edema; and atelectasis. Eight that died after a post-shock period of hyperventilation and hyperextension of the spine showed partial recovery of the pulmonary lesion; they showed well-expanded lungs, pleural petechiae, persistent congestion, with mild to moderate pathology. Mg-0 rats killed for study 2 days after the seizure-shock episode showed few small areas of residual lung pathology. Ultrastructural changes after Mg-O shock included aggregated platelets, leukocytes, and occasional reticulocytes in congested capillaries. Surfactant was disrupted during Mg-0 seizure-shock, but a layer closely applied to the surface of the epithelium was evident 2 days after shock. Mg-0 rats dying spontaneously showed nonspecific structural changes of the lung similar to changes reported in the sudden infant death syndrome (SIDS).
Magnesium 1988
PMID:Structural changes in lungs of magnesium-deficient weanling rats dying spontaneously or after spontaneous recovery from the seizure-shock episode. Possible methods for sudden infant death syndromes. 324 82


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