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)

The effect of potassium cyanide on mitochondria DNA (mtDNA) in mouse brain was investigated in vivo and in vitro. When potassium cyanide (0, 0.1, 1.0 or 2.0 mM) was incubated with a crude mitochondria fraction prepared from mouse brain at 37 degrees C for 60 min, the damage of mtDNA was observed in a concentration-dependent manner. However, the mtDNA damage was prevented by a co-treatment with melatonin (1.5 mM), a scavenger of hydroxyl radicals (*OH). Furthermore, a subcutaneous injection of potassium cyanide (7mg/kg) caused both brain mtDNA damage and severe seizures in mouse. The damage of mtDNA and seizures induced by potassium cyanide were abolished by the pre-injection of melatonin (20 mg/kg). Hydrogen peroxide (1.5 mM) inflicted damage to brain mtDNA in the presence of Fe(2+) (3.0 microM). The damage was abolished by the co-treatment with melatonin. Furthermore, when cyanide (0, 0.1 or 1.0 mM) was incubated with the crude mitochondria fraction prepared from mouse brain, the lipid peroxidation was significantly increased in a concentration-dependent manner. The increased lipid peroxidation was completely inhibited by the co-treatment with melatonin (1.0 mM). These results suggest that reactive oxygen species including the *OH may play a cardinal role for mtDNA damage induced by potassium cyanide. Hence, the present study concluded that melatonin protects against DNA damage induced by the *OH produced by cyanide or hydrogen peroxide.
 ...
PMID:Melatonin attenuates brain mitochondria DNA damage induced by potassium cyanide in vivo and in vitro. 1220 40

The goal of work was to reveal changes in microcirculation of the rat brain and the role of nitric oxide (NO) in development of seizures at hyperbaric oxygen exposure. The Wistar rats with implanted paired platinum electrodes in left and right striatum were used for experiments. The latency of seizures was defined by the EEG, the cerebral blood flow (CBF) was measured by hydrogen clearance. One group of animals was exposed to a 5-ata oxygen, while the others before oxygen treatment were injected with: Nw-nitro-L-arginine methyl ester (L-NAME), blockator of constitutive NO synthase; 7-nitroindozol (7NI), specific inhibitor of neural NO synthase. The latency of seizures was 41 +/- 1.9 min at 5 ata oxygen exposure. CBF was decreased to 10-14% but before seizures it increased to 23 +/- 9%. L-NAME and 7NI prevented development of hyperoxygen hyperemia and onset of seizures. The results indicate occurrence of hyperbaric oxygen changes of the CBF that modulate neurotoxic effects of NO in neurons as well as in cerebral vessels.
 ...
PMID:[Cerebral blood flow modulates hyperbaric oxygen induced neurotoxicity by neuronal and endothelial nitric oxide]. 1223 55

Overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors is closely related to epilepsy and excitotoxicity, and the phosphorylation of these receptors may facilitate glutamate-mediated synaptic transmission. Here we show that in awake rats the microinjection into the hippocampus of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, induces in about 20 min intense electroencephalographic and behavioral limbic-type seizures, which are suppressed by the systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine hydrogen maleate and by the intrahippocampal administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinases. Two hours after okadaic acid, when the EEG seizures were intense, an increased serine phosphorylation of some hippocampal proteins, including an enhancement of the serine phosphorylation of the NMDA receptor subunit NR2B, was detected by immunoblotting. Twenty-four hours after okadaic acid a marked destruction of hippocampal CA1 region was observed, which was not prevented by the receptor antagonists. These findings suggest that hyperphosphorylation of glutamate receptors in vivo may result in an increased sensitivity to the endogenous transmitter and therefore induce neuronal hyperexcitability and epilepsy.
 ...
PMID:Okadaic acid induces epileptic seizures and hyperphosphorylation of the NR2B subunit of the NMDA receptor in rat hippocampus in vivo. 1242 30

Zonisamide is an antiepileptic drug developed and first marketed in Japan in 1989. Cases of oligohydrosis, characterized by deficient production and secretion of sweat, were reported in children treated with zonisamide in Japan during development and in the postmarketing period. Zonisamide was approved in the United States in March 2000 for adjunctive treatment of partial seizures in adults. Searching the Food and Drug Administration's Adverse Events Reporting System, we identified six domestic cases of zonisamide-associated oligohydrosis and/or fever, all in patients </= 18 years of age. The calculated reporting rate was 13 cases per 10,000 pediatric-years of exposure, approximately 10-fold the reporting rate in Japan. A possible risk factor for the development of oligohydrosis in these cases was pediatric age, leading to exposure to elevated zonisamide blood levels relative to patient size. Although the mechanism for zonisamide-associated oligohydrosis has not been fully elucidated, the drug may mediate its effect on eccrine sweat glands by inhibiting carbonic anhydrase, thereby influencing pH dynamics, hydrogen ion concentration, and available calcium transients. Awareness of zonisamide-associated oligohydrosis may prevent morbidity, especially in the pediatric population.
 ...
PMID:Oligohydrosis and fever in pediatric patients treated with zonisamide. 1277 Jun 70

Conotoxin mr3a from the venom of Conus marmoreus, a novel peptide that induces rolling seizures in mice, has the peptide sequence GCCGSFACRFGCVOCCV, where O is trans-4-hydroxyproline, and the chain is cross-linked with disulfide bonds between Cys-2 and Cys-16, Cys-3 and Cys-12, and Cys-8 and Cys-15. The tertiary structure of mr3a was determined by 2D 1H NMR in combination with a standard distance-geometry algorithm. The final set of 22 structures for the peptide had a mean global backbone RMS deviation of 0.53 +/- 0.22 A based on 51 NOE, 6 hydrogen bond, 6 phi dihedral angle, and 3 disulfide bond constraints. Conotoxin mr3a is the first example of the new mini-M branch of conopeptides in the M superfamily. Members of the maxi-M branch, whose structures are known, include the mu- and psi-conotoxins, both of which share a common disulfide bond connectivity. Although mr3a has the same arrangement of Cys residues as the mu- and psi-conotoxins, its disulfide connectivity is different. This gives mr3a a distinctive "triple-turn" backbone.
 ...
PMID:Three-dimensional structure of the mini-M conotoxin mr3a. 1471 96

A series of p-nitrophenyl substituted semicarbazones (4a-c) and phenoxy/p-bromophenoxy acetyl hydrazones (8a-q) were synthesized and their anticonvulsant activity was screened against maximal electroshock seizure (MES), subcutaneous metrazole (ScMet) and subcutaneous strychnine (ScSty) tests. Compounds 4a-c with -NHCO- were found to be the most active in all these tests. These compounds were also active in the MES test after oral administration in rats. On the other hand, compounds 8a-q with -OCH2- were devoid of anticonvulsant activity. The studies revealed that the hydrogen bonding domain in semicarbazones, adjacent to the lipophilic aryl ring, is essential for the anticonvulsant activity.
 ...
PMID:Design and synthesis of semicarbazones and their bio-isosteric analogues as potent anticonvulsants: the role of hydrogen bonding. 1476 48

Sodium-hydrogen exchangers (NHEs) in the brain play a key role in regulating neuronal pH and, hence, modulate bioelectric and seizure activity. In this study, we investigated the anticonvulsant effect of amiloride (a NHE inhibitor) on increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizures in mice. Further, the effect of amiloride on mood, memory, grip strength, and rotarod performance was also evaluated. The forced swimming test (FST) and spontaneous alternation behavior (SAB) models were employed to assess the effects on mood and memory, respectively. Amiloride produced a dose-dependent increase in seizure threshold in both rodent models of epilepsy. It was observed that amiloride reduced behavioral depression in the FST in mice. In addition, it resulted in memory improvement in the SAB model. Amiloride did not affect grip strength and rotarod performance, suggesting it is devoid of behavioral impairment. The results indicate the potential antiseizure activity of amiloride along with additional neurological advantages.
 ...
PMID:Evidence of the antiepileptic potential of amiloride with neuropharmacological benefits in rodent models of epilepsy and behavior. 1514 1

The brain is deficient in oxidative defense mechanisms and hence is at greater risk of damage mediated by reactive oxygen species (ROS) resulting in molecular and cellular dysfunction. Emerging evidence suggesting the activation of glutamate gated cation channels, may be another source of oxidative stress, leading to neuronal degeneration. Oxidative stress has been implicated in the development of neurodegenerative diseases like Parkinsonism, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, epileptic seizures, and stroke. Melatonin, the pineal hormone, acts as a direct free radical scavenger and indirect antioxidant. It is suggested that the increase in neurodegenerative diseases is attributable to a decrease in the levels of melatonin with age. Melatonin has been shown to either stimulate gene expression for the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) or to increase their activity. Additionally, it neutralizes hydoxyl radical, superoxide radical, peroxyl radical, peroxynitrite anion, singlet oxygen, hydrogen peroxide, nitric oxide, and hypochlorous acid. Unlike other antioxidants, melatonin can easily cross all morphophysiological barriers, e.g., the blood brain barrier, and enters cells and subcellular compartments. Though evidence are accumulating to suggest the potential of melatonin in neurodegenerative conditions, much information needs to be generated before the drug can find place in neurology clinics.
 ...
PMID:Neuroprotective role of melatonin in oxidative stress vulnerable brain. 1526 48

Valproic acid (VPA), used to treat bipolar mood disorder and seizures, also inhibits histone deacetylase (HDAC). Here, we found that VPA and other HDAC inhibitors, butyrate and trichostatin A, robustly protected mature cerebellar granule cell cultures from excitotoxicity induced by SYM 2081 ((2S, 4R)-4-methylglutamate), an inhibitor of excitatory amino-acid transporters and an agonist of low-affinity kainate receptors. These neuroprotective effects required protracted treatment and were correlated with enhanced acetylated histone levels, indicating HDAC inhibition. SYM-induced excitotoxicity was blocked by MK-801 ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate), supporting that the toxicity was largely N-methyl-D-aspartate receptor dependent. SYM excitotoxicity had apoptotic characteristics and was prevented by a caspase inhibitor. SYM-induced apoptosis was associated with a rapid and robust nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene previously shown to be proapoptotic. VPA pretreatment suppressed SYM 2081-induced GAPDH nuclear accumulation, concurrent with its neuroprotective effects. Chromatin immunoprecipitation (ChIP) revealed that GAPDH is copresent with acetylated histone H3, including Lys9-acetylated histone, and that VPA treatment caused a time-dependent decrease in the levels of nuclear GAPDH with a concomitant increase in acetylated histones in the ChIP complex. Our results strongly suggest that VPA protects neurons from excitotoxicity through inhibition of HDAC activity and that this protective effect may involve suppression of excitotoxicity-induced accumulation of GAPDH protein in the nucleus.
 ...
PMID:Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. 1528 98

Normally, ventricular cerebrospinal fluid (CSF) contains low levels of all metabolite signals on proton magnetic resonance spectroscopic imaging (MRSI). We present here three cases (two with seizure disorders, one with a central nervous system lymphoma) who presented with unusually elevated CSF signals on MRSI. Based on chemical shifts and in vitro studies (in one case), the signals were assigned to propan-1,2-diol (PD), acetone, and lactate, respectively. These compounds were either exclusively, or more readily, detected in CSF than in brain. Proton MRSI conveniently screens both brain and CSF for abnormal metabolism simultaneously.
 ...
PMID:Metabolites in ventricular cerebrospinal fluid detected by proton magnetic resonance spectroscopic imaging. 1533 58


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