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

Magnesium sulfate is used for seizure prophylaxis in patients with preeclampsia. It also has significant effects on calcium metabolism and could, therefore, alter the pressor response to calcium-dependent vasoconstrictors. The present in vivo rat study examined the effect of magnesium sulfate to alter the pressor response to norepinephrine (NE) and angiotensin II (A II). Magnesium doses were chosen to approximate those used in treating preeclampsia. NE resulted in a significant rise in mean arterial pressure (delta MAP, 46 +/- 3.7 mmHg; p < 0.001). A II also resulted in a significant rise in MAP (delta MAP, 23 +/- 3.6 mmHg, p < 0.02). Magnesium sulfate alone had no significant effect on MAP but attenuated the pressor response to both NE (delta MAP, 16 +/- 1.5 mmHg) and A II (delta MAP, 12 +/- 2.5 mmHg). After discontinuation of the magnesium sulfate infusion, the control pressor responses to NE and A II were again seen (delta MAP, 39 +/- 3.5 mmHg and delta MAP, 28 +/- 4.2 mmHg, respectively). Although magnesium sulfate is not a primary antihypertensive agent, it may have effects on blood pressure by attenuating the actions of circulating vasoconstrictors.
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PMID:Effect of magnesium sulfate on the vascular actions of norepinephrine and angiotensin II. 141 60

Injection of kainic acid into rat induced a limbic seizure and increased the activities of two protein kinases with Mrs of 42 kDa and 44 kDa in the hippocampus. These two protein kinases were identified as MAP kinases by an anti-MAP kinase antibody. These MAP kinases were phosphorylated at least at a tyrosine residue. The time course of the MAP kinase activation was roughly parallel with that of the seizure. These results indicate that the kainic acid-induced seizure induces MAP kinase activation in rat hippocampus.
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PMID:Phosphorylation and activation of mitogen-activated protein kinase by kainic acid-induced seizure in rat hippocampus. 751 21

The immediate early gene-encoded enzyme, MAP kinase phosphatase 1 (MKP-1), is thought to be a key element in controlling cellular signalling pathways activated by MAP kinases. Since MAP kinase have been demonstrated to participate in neuronal stimulus-transcription coupling following seizure activity, the present study investigated the induction of MKP-1 in the rat brain after limbic epilepsy. MKP-1 expression was studied with a polyclonal antiserum by Western blots, immunocytochemistry and immuno-electron microscopy at different time periods between 1 and 24 h after kainic acid-induced limbic seizures. MKP-1 induction was identified in dentate granule cells of the hippocampus but not in pyramidal neurons, furthermore in neurons of the outer layers of the neocortex, as well as in neurons of the lateral nucleus of the bed of the stria terminalis. Immuno-electron microscopy demonstrated that MKP-1 was localized in the neuronal nucleus, where the substrate of MKP-1, activated MAP kinases, are also found. In view of the restricted areas of MKP-1 expression and the widespread areas of altered MAP kinases activity it can be concluded that in the majority of CNS populations other mechanisms than MKP-1 induction are responsible for the shut-off of MAP kinases following seizure activity. MKP-1 may contribute in the specific subpopulations where it is induced to the post-translational control of inducible transcription factors of the fos, jun and myc family.
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PMID:Transient expression of the mitogen-activated protein kinase phosphatase MKP-1 (3CH134/ERP1) in the rat brain after limbic epilepsy. 888 36

We have measured the effect of a bolus dose of esmolol 80 mg i.v. on heart rate, and systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures during electroconvulsive therapy (ECT). We also assessed seizure duration using both the cuff method and two-lead EEG. We studied 20 patients in a double-blind, placebo-controlled, within-patient blocked randomized study. No patient was receiving psychotherapeutic drugs or had cardiovascular disease. Esmolol significantly reduced heart rate, SAP and MAP before the stimulus, and also significantly reduced the increases in these variables during the convulsion, compared with placebo. However, seizure duration was also significantly reduced, possibly making ECT less effective. The reduction in seizure duration was 5.83 s when monitored clinically and 9.9 s when measured by the EEG. Because of the reduction in seizure duration, routine administration of esmolol is not advisable because it may interfere with the efficacy of ECT, but administration of esmolol during ECT could be useful to reduce tachycardia and hypertension in high-risk patients.
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PMID:Low-dose esmolol bolus reduces seizure duration during electroconvulsive therapy: a double-blind, placebo-controlled study. 1061 42

Pharmacological neuroprotection against the consequences of seizures can be considered as primary neuroprotection where the object is to diminish the initial insult by suppressing the seizure activity or diminishing the associated ionic fluxes (of which the entry of Na+ and Ca2+ are the most significant), and secondary neuroprotection where the target is some later event in the chain linking ionic changes to altered brain morphology or function. Thus primary neuroprotection is provided by antiepileptic drugs and compounds acting on voltage-sensitive Na+ and Ca2+ channels or on glutamate receptors (NMDA, AMPA/KA or Group I metabotropic). Secondary neuroprotection may be a result of acting on the cascade leading to necrosis (e.g. free radical scavengers, NitricOxide synthase inhibitors, CycloOxygenase-2 inhibitors) or the cascades leading to apoptosis (e.g. MAP-kinase inhibitors, caspase-3 inhibitors). Other approaches may diminish the long-term morphological and functional effects of seizures (e.g. neurotrophin-related therapies). We need improved preclinical tests for identifying novel compounds with potential for providing secondary neuroprotection and antiepileptogenesis. Clinical trials of neuroprotective agents in chronic epilepsy in adults pose major practical difficulties but the severe childhood epilepsies provide opportunities for aggressive testing of novel compounds.
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PMID:Implications for neuroprotective treatments. 1214 67

Asphyxia in utero in pre-term fetuses is associated with evolving hypoperfusion of the gut after the insult. We examined the role of the sympathetic nervous system (SNS) in mediating this secondary hypoperfusion. Gut blood flow changes were also assessed during postasphyxial seizures. Preterm fetal sheep at 70% of gestation (103-104 days, term is 147 days) underwent sham asphyxia or asphyxia induced by 25 min of complete cord occlusion and fetuses were studied for 3 days afterwards. Phentolamine (10 mg bolus plus 10 mg h(-1)i.v.) or saline was infused for 8 h starting 15 min after the end of asphyxia or sham asphyxia. Phentolamine blocked the fall in superior mesenteric artery blood flow (SMABF) after asphyxia and there was a significant decrease in MAP for the first 3 h of infusion (33 +/- 1.6 mmHg versus vehicle 36.7 +/- 0.8 mmHg, P < 0.005). During seizures SMABF fell significantly (8.3 +/- 2.3 versus 11.4 +/- 2.7 ml min(-1), P < 0.005), and SMABF was more than 10% below baseline for 13.0 +/- 1.7 min per seizure (versus seizure duration of 78.1 +/- 7.2 s). Phentolamine was associated with earlier onset of seizures (5.0 +/- 0.4 versus 7.1 +/- 0.7 h, P < 0.05), but no change in amplitude or duration, and prevented the fall in SMABF. In conclusion, the present study confirms the hypothesis that postasphyxial hypoperfusion of the gut is strongly mediated by the SNS. The data highlight the importance of sympathetic activity in the initial elevation of blood pressure after asphyxia and are consistent with a role for the mesenteric system as a key resistance bed that helps to maintain perfusion in other, more vulnerable systems.
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PMID:The role of the sympathetic nervous system in postasphyxial intestinal hypoperfusion in the pre-term sheep fetus. 1507 76

For the development of rabbit models of Systemic Lupus Erythematosus (SLE), immunoglobulin allotype-defined pedigreed rabbits from the National Institute of Allergy and Infectious Diseases rabbit resource more closely approximate human populations due to their non-inbred pedigreed structure. In an initial study from this laboratory, peptides (SM and GR) from the spliceosomal Smith (Sm) and the NMDA glutamate receptor NR2b, on branched polylysine backbones (BB) elicited antinuclear and anti-dsDNA autoantibodies typical of SLE, as well as seizures and nystagmus sometimes observed as neurological manifestations in SLE patients. This suggested the feasibility of further selective breeding to develop a more reproducible rabbit model for investigations of SLE. Here we report the results of GR-MAP-8 and control BB immunization on autoantibody responses in a group of 24 rabbits specifically bred and developed from parents and ancestors tested for autoantibody responses. The changes in hematological profile and blood chemistry in the experimental rabbits were evaluated along with autoantibody responses. Elevations of total white blood cell (WBC), monocyte, eosinophil and basophil counts that developed following immunizations were moderately influenced by litter and presence of the antibody heavy chain allotype VH1a1. Autoantibody development followed a sequential pattern with anti-nuclear antibodies (ANA) followed by anti-dsDNA and subsequently anti-Sm and anti-RNP similar to SLE patients. High autoantibody levels to one autoantigen were not always associated with antibody response to another. Female rabbits had higher prevalence and levels of autoantibodies similar to human SLE. Higher autoantibody levels of anti-dsDNA and -ANA were observed among some full sibs and the presence of high responder ancestors in the pedigree was associated the augmented responses. We observed significant association between highest antibody responses to GR-MAP-8 and highest anti-dsDNA levels. Naturally occurring autoantibodies were found in some pre-immune sera and some unique ANA fluorescent staining patterns within the experimental group were observed. Background immunofluorescence in pre-immune sera, distinct patterns of programmed autoantibody responses unique among individual rabbits may have been modulated by genetic constitution, gender and environmental factors including exposure to antigens. The high incidence and intensity of autoantibody responses among descendants of high responders suggest that there may be an additive mode of inheritance with high heritability. It is conceivable that further rigorous pedigree selection for autoantibody responses could lead to development of rabbit models with spontaneous occurrence of SLE like serology and disease phenotypes.
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PMID:Genetic contributions to the autoantibody profile in a rabbit model of Systemic Lupus Erythematosus (SLE). 1860 65

Nestin is one kind of intermediate filament protein, which is considered as a typical marker of neural precursor cells. Considerable evidence supports nestin may have actively functions in neurogenesis and gliosis. Our aim was to investigate nestin expression in the temporal neocortex of patients with intractable epilepsy (IE), and then to discuss the possible role of nestin in IE. Tissue samples from the temporal neocortex of 32 patients who had surgery for IE were used to detect nestin expression by immunohistochemistry, immunofluorescence. We compared these tissues with 12 histologically normal temporal neocortex from intracranial hypertension patients who had decompression procedures. In this study, we found some nestin positive cells in the normal temporal neocortex, but in the intractable epilepsy, they were upregulated, increasing with length of course and seizure frequency. Optical density (OD) value in epileptic tissue was determined 0.246 +/- 0.030, and 0.134 +/- 0.040 in the control (P < 0.05). Double lables of immunofluorescence showed some nestin positive cells coexpression with glial fibrillary acidic protein (GFAP), while some coexpression with microtubule-associated protein-2 (MAP(2)). These findings provided some evidence for increased neurogenesis and gliosis in epilepsy, which could be associated with intractable epilepsy.
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PMID:Nestin in the temporal neocortex of the intractable epilepsy patients. 1871 94

Repeated seizures induce permanent alterations of the brain in experimental models and patients with intractable temporal lobe epilepsy (TLE), which is a common form of epilepsy in humans. Together with cell loss and gliosis in many brain regions, synaptic reorganization is observed principally in the hippocampus. However, in the amygdala this synaptic reorganization has been not studied. The changes in Zn density, synaptophysin and MAP(2) as markers of reactive synaptogenesis in medial extended amygdala induced by kainic acid (KA) as a model of TLE was studied. Adult male rats (n=6) were perfused at 10 days, 1, 2, 3 and 4 months after KA i.p. injection (9 mg/kg). Controls were injected with saline. The brains were processed by the Timm's method to reveal synaptic Zn and analyzed by densitometry. Immunohistochemistry was used to reveal synaptophysin and MAP(2) expression. A two-way ANOVA was used for statistics, with a P<0.05 as a significance limit. Normal dark staining was seen in all medial extended amygdala subdivisions of control animals. At 10 days post KA injection a dramatic loss of staining was observed. A slow but steady recovery of Zn density can be followed in the 4 month period studied. Parallel, from 10 days to 2 months stronger synaptophysin expression could be observed, whereas MAP(2) expression increased from 1 month with peak levels at 3-4 months. The results suggest that a process of sprouting exists in surviving neurons of medial extended amygdala after status epilepticus and that these neurons might be an evidence of a reactive synaptogenesis process.
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PMID:Timed changes of synaptic zinc, synaptophysin and MAP2 in medial extended amygdala of epileptic animals are suggestive of reactive neuroplasticity. 2014 92

We report a rare case of focal cortical dysplasia (FCD) concurring with diffuse astrocytoma and arachnoid cyst, and also re-evaluate the glial component in archival FCD cases for the differential diagnosis of diffuse gliomas. A 7-year-old boy with a 9-month history of psychomotor seizures disclosed a hyperintense area accompanied by a cystic lesion in the left temporal lobe on MRI. The surgical specimen displayed dyslamination of the cortices and ectopic neurons in the white matter, associated with dysmorphic neurons, indicating FCD type IIA. Additionally, the lesion showed diffuse proliferation and infiltration of glial cells, immunopositive for infiltrating glioma markers (nestin, doublecortin, MAP-2e) and p53, and MIB-1 index was 2.0%. These findings indicated coexisting diffuse astrocytoma. Coexistence of diffuse glioma with FCD is unusual, but we often notice increased population of small glial cells in FCD lesions. Re-evaluation of archival FCD cases with diverse markers revealed that reactive microglia significantly proliferate in the white matter lesions. Therefore, a careful pathological assessment has to be made to define a rare case of diffuse glioma occurring in FCD.
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PMID:Focal cortical dysplasia coexisting with diffuse astrocytoma in childhood: a case report and reappraisal of the glial component in archival FCD cases. 2111


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