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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unilateral intrastriatal injection of quinolinic acid (2,3 pyridine dicarboxylate; QUIN) in the rat produces episodic barrel rotations and tonic-clonic forepaw movements, lasting for several hours. We investigated whether intraperitoneal posttreatment with anticonvulsants could abolish this phenomenon when it is already fully developed, and whether their potency ratio was similar in models of epilepsy. All 8 tested antiepileptics, namely carbamazepine, clonazepam, diazepam, diphenylhydantoin, ethosuximide, flunarizine, phenobarbital and sodium valproate decreased this behaviour in a dose-dependent way. Six other drugs with anticonvulsant properties were also effective: DL-2-amino-7-phosphonoheptanoic acid, desipramine, etomidate, ketamine, meprobamate and sabeluzole. The ED50-values for halving the frequency of the episodes of barrel rotation correlated well with published ED50-values for inhibition of tonic hindpaw extension in the maximal metrazol seizure test (rs = .95, p less than 0.001) and with the ED50-values for halving the duration of the forepaw clonus in the rat-kindling model (rs = .93, p less than 0.001). This quinolinic acid test allows visualization of the onset of action of anticonvulsants, with each animal as its own control. In order to assess whether this test is also sensitive to drugs influencing the symptoms of Huntington's disease, the effect of the dopamine antagonists haloperidol and pimozide, the acetylcholinesterase inhibitor physostigmine and the anticholinergics atropine and dexetimide were investigated as well. The experiments suggested that the barrel rotations and clonic forepaw movements, only 3-6 hours after intrastriatal injection of QUIN respond to anticonvulsants, but are not specifically sensitive to drugs used in the symptomatic treatment of Huntington's disease.
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PMID:Episodic barrel rotations induced by intrastriatal injection of quinolinic acid in rats. Inhibition by anticonvulsants. 297 64

The effects of acute exposure to acrylonitrile (ACN), 10, 20, or 40 mg/kg by gavage, on the ability of metrazol (MTZ) to induce seizures was studied in adult, male Sprague-Dawley rats. The frequency of seizure occurrence and the frequency of a lethal seizure was greater when the high ACN dosage was given in combination with metrazol. This dosage of ACN was not lethal when given alone. Examination of brain tissue in these animals revealed no difference in cyanide levels when MTZ was combined with ACN. However, brain cytochrome c was significantly lower in animals given ACN+MTZ and brain cholinesterase was significantly higher. These results suggest that the enhanced lethality occurring in animals exposed to the combination of ACN+MTZ is not due to cyanide, a metabolic product of ACN, but rather to a potentiation of other effects of ACN perhaps involving cholinergic neurotransmission.
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PMID:Effect of acute acrylonitrile exposure on metrazol induced seizures in the rat. 298 62

Seizure-experienced Genetically Epilepsy-prone Rats (GEPRs) have increased acetylcholine content and choline acetyltransferase activity in the thalamus and striatum. These cholinergic differences are accompanied by a slight but statistically significant reduction in acetylcholinesterase activity in the midbrain. In addition, no abnormalities were found in the numbers of specific 3H-QNB binding sites in the striatum, hippocampus, inferior colliculi or cortex. Other work has shown no difference in muscarinic receptor function as measured by carbachol-stimulated inositol-1-phosphate formation. These data suggest a possible presynaptic defect in the striatal and thalamic cholinergic system which may play some role in the seizure-prone state of the GEPR. However, caution must be used in interpreting these cholinergic derangements since more recent findings show no differences in thalamic acetylcholine content in seizure-naive GEPRs. Thus, the original cholinergic abnormalities detected in the seizure-experienced GEPR may be an enduring response to seizure activity.
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PMID:Abnormalities in the central cholinergic transmitter system of the genetically epilepsy-prone rat. 301 14

Central effects of paraoxon (an organophosphate, inhibitor of acetylcholinesterase) treatment were investigated using 2-deoxyglucose (2-DG) and EEG methods. Six rat brain structures (external globus pallidus, ventral anterior nucleus of thalamus, entopeduncular nucleus, substantia nigra pars reticulata and superior colliculus) presented an increase of 2-DG labelling after acute injection of this toxic compound. The EEG recordings showed hippocampal slow theta rhythm which preceded an increase of cortical rhythm frequency. Rats with 2-DG mapping modifications presented also EEG seizures.
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PMID:Selective activation of striatal output nuclei by organophosphorus intoxication in the rat: EEG and 2-deoxy[3H]glucose metabolic mapping. 318 66

The clinical and laboratory features of moderate to severe organophosphate and carbamate toxicity in 37 infants and children are presented. Ingestion of an improperly stored liquid pesticide was the most common route of intoxication (76% of patients); five (14%) children became intoxicated after playing on carpets and floors of homes that had been sprayed or fogged by unlicensed exterminators. The transfer diagnoses were incorrect for 16 or 20 patients who were transferred to our center from another institution. Miosis (73%), excessive salivation (70%), muscle weakness (68%), and lethargy (54%) were the most common abnormal signs; 49% and 22% of patients had tachycardia and seizures, respectively, and 38% of children had respiratory insufficiency that required endotracheal intubation and mechanical ventilation. The results of erythrocyte and serum cholinesterase activity assays were concordant in 83% of patients. Thirty-four (92%) patients were treated with atropine and/or pralidoxime; three patients required only supportive care. Most patients had a prompt response to therapy; however, two patients with organophosphate toxicity required multiple doses of atropine during a 24-hour period; in both instances, the doses of atropine were subtherapeutic. There were no deaths. Pneumonitis and/or atelectasis developed in ten patients, including six who had ingested a petroleum distillate-containing insecticide.
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PMID:Organophosphate and carbamate poisoning in infants and children. 333 78

The development of kindled seizures elicited through electrical stimulation of the rat olfactory bulb (OB) was examined under two conditions which decrease cholinergic neurotransmission. Atropine sulfate (25 mg/kg, IP) administered 1 hr prior to stimulation of the OB was found to significantly delay the acquisition of the fully kindled state. In a second experiment, diminished cholinergic innervation of the OB was established using chemical lesions of the basal forebrain cholinergic system. Despite the depletion of acetylcholine (Ach), as determined by acetylcholinesterase (AchE) and choline acetyltransferase (ChAt) assays, no significant alterations in kindling parameters were observed. Based upon these findings we suggest that Ach is not critical to the establishment of an OB kindled focus but is important for the propagation and generalization of epileptiform activity initiated through OB stimulation.
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PMID:Atropine slows olfactory bulb kindling while diminished cholinergic innervation does not. 337 May 4

Rats treated intravenously with an organophosphorus anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7 sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucose as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8 LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2 hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.
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PMID:Cerebral metabolic effects of organophosphorus anticholinesterase compounds. 350 39

Most childhood exposures to insecticides and herbicides do not result in poisonings. Decontamination and observation are usually adequate treatments. The most frequent exposures involve carbamate and organophosphate insecticides. These compounds inhibit acetylcholinesterase, resulting in cholinergic signs that are reversible with atropine administration. Recent reports from poison control centers indicate that organophosphates have been associated with most of the serious childhood poisonings. Pralidoxime, a cholinesterase reactivator, must be administered along with atropine to patients with serious organophosphate poisoning, to reverse nicotinic receptor effects--in particular, respiratory paralysis. Although carbamates and organophosphates may cause clinically indistinguishable physical signs, pralidoxime therapy may be contraindicated for carbamate intoxications. In the event of a serious poisoning caused by a combination of organophosphate and carbamate insecticides, or by an unknown cholinergic agent, pralidoxime should not be withheld. Many organochlorine insecticides are restricted or are no longer available in the United States. CNS excitation and seizures, manifestations of organochlorine intoxication, can occur following ingestion or inappropriate application of the 1 per cent topical formulation of lindane used to treat scabies and lice. Treatment of such intoxication consists of decontamination measures and anticonvulsant administration. Pyrethrins are generally nontoxic in doses commonly ingested. Individuals with an allergic history may be at greatest risk for the most common adverse effects, contact dermatitis and hypersensitivity reactions. Of all insecticides or herbicides, paraquat is the most toxic. Any exposure to paraquat must be evaluated, even if several days have passed since the herbicide was ingested. Signs of pulmonary status deterioration usually portend a grave prognosis in paraquat poisoning. Despite in vitro toxicity similar to paraquat, diquat does not cause lung effects in human poisonings, and reported deaths have been from other causes. Poisoned patients who receive appropriate and timely treatment are virtually assured of complete recovery from most insecticide and herbicide poisonings. Deaths and long-term sequelae most often result from respiratory complications, which may occur as complications of the intoxication or from other constituents in the insecticide or herbicide formulation. Good supportive care with meticulous attention to, and anticipation of, respiratory complications is absolutely essential to prevent long-term sequelae or death from hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Management of acute childhood poisonings caused by selected insecticides and herbicides. 351 3

Rats injected with a nonlethal acute dose (100 micrograms/kg, sc) of soman (pinacolyl methylphosphonofluoridate) exhibited signs of anticholinesterase toxicity beginning at 5-15 min with increasing severity and lasting for 4-6 hr. Generalized tremors and seizure activity indicated comparatively greater involvement of the central cholinergic system than peripheral neuromuscular effects. During peak toxicity, all the brain regions tested showed more than 95% inhibition of acetylcholinesterase (AChE) activity. The cortex area was maximally affected (99% inhibition). Among skeletal muscles, soleus AChE was most severely affected (94%) and extensor digitorum longus (EDL) the least (72%). Inhibition of EDL AChE occurred at a much slower rate than in brain and other muscles. Significant recovery of AChE activity was seen by 48-72 hr after soman treatment in both brain and skeletal muscles. By Day 7, recovery was virtually complete in skeletal muscles but not in brain, although significant recovery had occurred by this time. Muscle fiber necrosis developed within 6 hr in the soleus and diaphragm, while no necrotic fibers were found in the EDL. The 16 S AChE molecular form showed the fastest recovery of the AChE isozymes in all three muscles. Full recovery was seen after 7 days in soleus and was increased to greater than control activity in diaphragm and EDL. The inhibition pattern of butyrylcholinesterase (BuChE) activity was similar to that described for AChE activity, but the recovery was comparatively faster. Carboxylesterase activity in plasma was decreased to less than 10% of control within 1 hr and recovered to 53% of control within 24 hr. No significant inhibition was seen in hepatic carboxylesterase activity. It can be concluded that soman-induced acute toxicity is directly related to the rate and degree of AChE inhibition. A significant amount of soman binds to non-AChE enzymes with serine sites such as BuChE and carboxylesterases.
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PMID:Biochemical and histochemical alterations following acute soman intoxication in the rat. 356 14

The activity of acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF) of rats increased by 53% following an electroconvulsive shock (ECS) while non-specific cholinesterase (nsChE) activity was unchanged. A flurothyl-induced seizure failed to elicit a change in the AChE activity of CSF. A bilateral lesion of the substantia nigra pars reticulata abolished the rise in AChE activity in the CSF but did not diminish the increase of seizure threshold which follows a convulsion. These data suggest that AChE is released from the substantia nigra following a seizure but indicate that the change is not associated with the rise in seizure threshold which occurs.
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PMID:Acetylcholinesterase activity rises in rat cerebrospinal fluid post-ictally; effect of a substantia nigra lesion on this rise and on seizure threshold. 359 73


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