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)

Subtractive library construction and differential screening were used to identify a cDNA for a cell type-specific immediate early gene induced in rat PC12 pheochromocytoma cells. Sequencing identified the protein product of this gene as rat synaptotagmin IV (SytIV). Synaptotagmins are synaptic vesicle proteins thought to play a role in depolarization-induced, calcium-mediated exocytosis and neurotransmitter release. SytIV mRNA accumulation is transiently induced in PC12 cells by potassium depolarization, calcium ionophore, ATP, and forskolin. In contrast, growth factors and phorbol 12-myristate 13-acetate induce little or no SytIV mRNA accumulation. Kainic acid-induced seizures in rats are followed by accumulation of SytIV message in the hippocampus and piriform cortex. The SytIV gene may provide a direct link between depolarization-induced neuronal gene expression and subsequent modulation of synaptic structure and function.
 ...
PMID:Synaptotagmin IV is an immediate early gene induced by depolarization in PC12 cells and in brain. 789 40

The dynamic effects of the non-competitive NMDA receptor antagonist, MK-801 on brain metabolism were investigated over 105 minutes in unanesthetized rats by proton and phosphorus NMR spectroscopy. MK-801 (0.5 and 5 mg/kg, i.p) induced no changes in intracellular pH, and in phosphocreatine, ATP, and inorganic phosphate levels, indicating that the drug preserved energy and intracellular pH homeostasis. There were transient increases in lactate after both doses of MK-801, suggesting early activation of glycolysis, which was not immediately matched by enhanced oxidative metabolism or by enhanced blood flow. Thereafter, lactate control level was not restored after 0.5 mg/kg whereas it was restored after 5 mg/kg in spite of a sustained metabolic activation. The low dose of MK-801 also caused a continuous decrease in cerebral aspartate level (-38%) which is thought to match the enhanced energy demand, whereas the high dose caused shorter and smaller changes. The intracerebral glucose level rose after MK-801 injection, indicating that brain tissue had an adequate or even excessive supply of glucose. Glucose time course seemed to closely match the changes in blood flow elicited by MK-801. This is the first study giving the metabolic pattern of a pharmacological activation. We demonstrate an excess of glycolysis over oxidative metabolism in the early time similar to that following physiological and pathophysiological states such as photic stimulation and seizures. The difference between the effects of the two doses of MK-801 suggests that the adjustment of cerebral metabolism to MK-801 activation is faster and greater with the high dose than with the low dose.
 ...
PMID:Cerebral metabolic changes induced by MK-801: a 1D (phosphorus and proton) and 2D (proton) in vivo NMR spectroscopy study. 803 9

A Ca(2+)- or Mg(2+)-stimulated ecto-ATPase is thought to regulate the hydrolysis of extracellular ATP in nervous tissues. The hydrolysis of nucleotide triphosphates (NTPs) was analyzed in brain microsomal fractions from crosses of DBA/2J (D2) and C57BL/6J (B6) mice. The nucleotide triphosphatase (NTPase) activity was significantly reduced in D2 mice as compared to B6 mice, and B6D2F1 hybrids had activities intermediate to the parentals. A significant positive correlation was found between the hydrolysis of four NTPs (ATP, CTP, GTP and UTP) in 24 B6 x D2 (BXD) recombinant inbred (RI) strains of mice and in 80 B6D2F1 x D2 backcross mice. The RI strains and backcross mice fell into two distinct groups with respect to the NTPase activity. Linkage of NTPase activity was suggested with the chromosome 2 markers, D2Mit6 and Ass-1, in the RI strains, and was confirmed by analysis of other markers in the backcross population. These data suggest that the Ca(2+)- or Mg(2+)-stimulated hydrolysis of NTPs, designated Ntp, is regulated by a single gene located on proximal chromosome 2. Although an association was observed previously between Ca(2+)-ATPase activity and susceptibility to audiogenic seizures (AGS), no significant association was observed for the expression of Ntp and AGS susceptibility.
 ...
PMID:Genetic analysis of nucleotide triphosphatase activity in the mouse brain. 805 15

Seizures were induced in 7-day-old rats by intraperitoneal injection of DL-homocysteine thiolactone. Phosphocreatine (PCr), ATP, glucose, glycogen and lactate were determined in the cerebral cortex during various intervals after injection, corresponding to the early, as well as long periods of seizure activity. The unchanged levels of ATP, a very mild PCr decline and a pronounced accumulation of lactate (in the face of modest changes in brain glucose and glycogen) were observed. These results suggest that the immature rat brain is able to compensate energy expenditure associated with seizure activity by increased energy production, mainly due to increased anaerobic glycolysis. It remains to be determined whether a similar conclusion is also valid for other brain regions, e.g. subcortical structures.
 ...
PMID:Cerebral energy state of neonatal rats during seizures induced by homocysteine. 818 Jan 46

The cerebral metabolic changes elicited by kainate-induced seizures in the rat were investigated by in vivo combined NMR spectroscopy of 31P and 1H. Systemic injection of kainate induced no significant changes in cerebral ATP or PCr levels during up to 90 min of continuous, generalised seizures, and the cerebral 31P spectra showed only a transient mild cerebral acidosis 30 min after kainate administration. In parallel with the changes in intracellular cerebral pH, the 1H spectra showed a significant increase in lactate, which remained elevated throughout the seizures. These findings indicate that oxidative metabolism does not completely match the increased glycolysis during seizures though the energy homeostasis is maintained. This suggests that oxidative metabolism has a limited capacity to satisfy the brain's energy needs during the kainate-induced seizures, but that the different pathways of energy production in the brain cells can overcome this limitation. Thus the brain damage associated with this experimental model of epilepsy is not due to extended major failure of the energy supply.
 ...
PMID:Effects of kainate-induced seizures on cerebral metabolism: a combined 1H and 31P NMR study in rat. 819 76

Seizures were induced in 7-day-old rats by intraperitoneal injection of DL-homocysteine thiolactone. Phosphocreatine (PCr), ATP, glucose, glycogen and lactate were determined in the cerebral cortex during various intervals after injection, corresponding to the early, as well as long periods of seizure activity. The unchanged levels of ATP, a very mild PCr decline and a pronounced accumulation of lactate (in the face of modest changes in brain glucose and glycogen) were observed. These results suggest that the immature rat brain is able to compensate energy expenditure associated with seizure activity by increased energy production, mainly due to increased anaerobic glycolysis. It remains to be determined whether a similar conclusion is also valid for other brain regions, e.g. subcortical structures.
 ...
PMID:Cerebral energy state of neonatal rats during seizures induced by homocysteine. 821 46

Previous studies suggested that hypoxia reduces the severity of brain injury after epileptic seizures. To test this hypothesis, the effect of hypoxic arrest of epileptic seizures on brain metabolism was investigated in rats by combining in vivo NMR spectroscopy with imaging techniques for the pictorial evaluation of energy metabolism and pH. Seizures were produced by i.v. injection of bicuculline, and measurements were compared in animals with and without 5 min exposure to 5% oxygen after the onset of seizures. Transient hypoxia persistently reduced seizure activity, even after return to normoxia. Hypoxia or seizure alone had little effect on brain metabolism but the combination of both led to marked albeit reversible deterioration of energy and acid/base status. In normoxic animals pictorial measurements of energy state 2 h after the onset of seizures revealed a regional decline of ATP in the hippocampus. In animals in which seizures were arrested by transient hypoxia ATP depletion was additionally observed in the border zones of vascular territories. These results demonstrate that hypoxic arrest of seizure activity leads to the aggravation of metabolic disturbances and is therefore not suited to preventing permanent brain injury.
 ...
PMID:Effect of hypoxia on bicuculline seizures of rat: NMR spectroscopy and bioluminescence imaging. 826 66

Specific probes were obtained using PCR cloning from rat brain for the 78 kDa glucose regulated (grp78), inducible 72 kDa (hsp70) as well as constitutive 73 kDa (hsc73) heat shock mRNAs. Grp78 and hsc73 were expressed in normal rat brain whereas hsp70 was not. Subcutaneous injection kainic acid (10 mg/kg) produced seizures and induced all three mRNAs. The induction of grp78 and hsp70 mRNAs occurred within 2 h, peaked between 6-8 h, persisted for 48 h, and returned to control levels by 72 h. Expression of the grp78 and hsp70 mRNAs after focal ischemia progressively increased with occlusion durations from 15-120 min in the cerebral cortex. Though grp78 and hsp70 mRNAs were induced modestly in the striatum by 15 min of ischemia, longer durations of ischemia were characterized by little change in the grp78 mRNA levels and relatively lower levels of hsp70 expression. This result indicates that progressive increases in the duration of ischemia in brain, prior to infarction, may produce proportional increases in transcription of the heat shock genes. However, once the duration of ischemia is long enough to produce infarction, this severely limits the availability of ATP which blocks transcription of the heat shock genes. In conclusion, concurrent induction of the heat shock genes suggests that kainic acid seizures and focal ischemia induce several different stress responses in brain cells caused by denaturation of proteins, changes of protein synthesis, and changes of protein glycosylation.
 ...
PMID:Induction of glucose regulated protein (grp78) and inducible heat shock protein (hsp70) mRNAs in rat brain after kainic acid seizures and focal ischemia. 828 Nov 26

Although L-carnitine has been reported to have protective effects against ammonia toxicity, conflicting results have also been presented and the mechanisms underlying the protection, if any, are not clear. In the present study, we examined the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Administration of ammonium acetate (15 mmol/kg) to mice caused seizures, elevation of blood ammonia and urea concentrations, and marked alterations of brain energy metabolites. Pretreatment with either L-carnitine, D-carnitine or acetyl-L-carnitine reduced the frequency of the seizures, prolonged the time until the first fit, lowered the levels of ammonia in the blood and brain, and suppressed the alterations of brain energy metabolites caused by hyperammonemia. there was no significant difference between L- and D-carnitine in the potency to inhibit the seizures. In addition, there was no difference between the two chemicals in the potency to decrease the ammonia contents in the blood and brain, or to suppress the alterations of energy metabolites in the brain. When compared with L-carnitine, however, acetyl-L-carnitine better preserved ATP in the brain, while it lowered ammonia in the blood and brain less markedly. These results show that L-carnitine and its analogues do have the potential to suppress the neurotoxicity of ammonia. Moreover, the results suggest that the protective effects of carnitine against the toxicity of ammonia are systemic, that the action of acetyl-L-carnitine may differ from that of L- or D-carnitine, and that the "classical" function of carnitine is not the sole mechanism underlying the suppression of the neurotoxicity of ammonia.
 ...
PMID:Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. 834 26

Previous studies in our laboratory have shown that L-carnitine suppresses seizures and alterations of brain energy metabolism in mice caused by hyperammonemia. The present study was done to exclude the effects of seizures on brain energy metabolism. When sublethal dose of ammonium acetate (12 mmol/kg b.wt.) was injected to mice, all mice survived without developing seizures, while clear increase of brain ammonia and alterations of brain energy metabolites were seen. In L-carnitine-treated animals, the levels of ammonia, AMP and lactate were lower and those of ATP and phosphocreatine were higher than in untreated animals. Treatment with D-carnitine also preserved the phosphocreatine level. This indicates that the improvement of brain energy metabolism by L-carnitine in hyperammonemia is not simply a result of the suppression of seizures, and that the "physiological" function of carnitine may not be the sole mechanism underlying this effect.
 ...
PMID:Effects of L and D-carnitine on brain energy metabolites in mice given sublethal doses of ammonium acetate. 851 63


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