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

The acute effects of diisopropylfluorophosphate (DFP) were assessed in DBA/2Ibg, C57BL/6Ibg and C3H/2Ibg mice. The DFP was administered by intraperitoneal injection in saline. Brain acetylcholinesterase (AChE) activity was maximally inhibited within 5 min after injection. All mice showed signs of organophosphate intoxication including salivation, lacrimation, diarrhea, respiratory distress, tremor and, at high doses, seizures. The C57BL mice were most susceptible to these effects of DFP. The LD50 values for DFP were 8.0, 7.6, and 6.8 mg/kg for male DBA, C3H, and C57BL mice, respectively. The LD50 values for females were nearly the same. Body temperature and brain AChE activity decreased in a dose-dependent manner following injections of DFP of 3.17, 4.22, 5.28, and 6.33 mg/kg. Maximum temperature depression occurred 2 hours after DFP administration; by 24 hours temperatures had returned to normal except for C57BL mice treated with the highest dose of DFP. The C57BL strain was most susceptible to the DFP-induced hypothermia, the C3H strain was the most resistant, and the DBA strain was intermediate. Maximum temperature depression and residual AChE activity, as measured 24 hours after injection, were linearly related. These strain differences do not seem to be explained easily by a differential inhibition of AChE activity.
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PMID:Genetically determined differences in acute responses to diisopropylfluorophosphate. 399 71

The kindling phenomenon was produced after chronic electrostimulation of the cat amygdala. The duration and intensity of petit mal and grand mal were recorded. The M-cholinomimetic arecoline (0.3 mg/kg), the acetylcholinesterase inhibitor galanthamine (1-3 mg/kg) and the N-cholinergic blockers eterofen (5-10 mg/kg) and ganglerone (035-3.5 mg/kg) intraperitoneally decreased or abolished the kindling phenomenon. Combination of M-cholinomimetics with N-blockers facilitated the anticonvulsant effects. Nicotine (0.5 mg/kg) and the M-cholinergic blocker methylbenactyzine (0.5-1 mg/kg) as well as combination of methylbenactyzine with galanthamine, on the contrary, facilitated and aggravated seizures in cats. In the authors' opinion, the M- and N-cholinergic mechanisms are involved in formation of the kindling phenomenon. It is suggested that N-cholinergic blockers or their combinations with M-cholinomimetics may be used as anticonvulsants.
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PMID:[Participation of m- and n-cholinergic mechanisms in the development of the kindling phenomenon of the amygdala in cats]. 400 13

Male juvenile baboons, trained on a match-to-sample operant discrimination task, were given acute intramuscular injections of soman (methyl pinacolyl phosphonofluoridate) at 1.0, 2.0, 3.0, 4.0, and 5.0 micrograms/kg. The different doses were given in a mixed order just before a behavioral test session. Just prior to administration of each soman dose and immediately following the 2-hr behavioral test session, a sample of blood (0.5 ml) was drawn from the baboon and analyzed for inhibition of acetylcholinesterase activity. Thereafter, blood sampling was accomplished at weekly intervals and soman was administered again only when whole blood acetylcholinesterase reached at least 80% of pre-soman control level. Behavioral effects of soman included a slowing of response times, a decrease in extra inconsequential responses, a decrease in responsiveness to the visual stimuli and an increase in errors. These effects were observed when acetylcholinesterase (AChE) levels fell to 25 mumoles/hr/ml blood or less. The threshold dose for behavioral effects was very close to the dose of soman which induced seizures.
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PMID:Acute soman effects in the juvenile baboon: effects on a match-to-sample discrimination task and on total blood acetylcholinesterase. 402 28

Rats were trained to press a lever under a multiple fixed-ratio 25 fixed-interval 50-second (FR25 FI50-sec) schedule of food reinforcement. Soman, 70-90 micrograms/kg, s.c., suppressed response rates in both components, with a slightly greater effect in the FI schedule. The pattern of responding under the FI schedule, however, was maintained until lever-pressing was nearly completely suppressed. At the highest doses, soman occasionally caused tremors or mild tonic seizures with hindlimb abduction. The suppression of response rate was correlated with inhibition of acetylcholinesterase (AChE) in all brain regions examined: cortex, striatum, hippocampus, hypothalamus and brainstem. Cortical AChE was inhibited to the highest degree, while striatal AChE was most resistant to inhibition by soman.
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PMID:Effect of soman on schedule-controlled behavior and brain acetylcholinesterase in rats. 407 56

Juvenile male baboons were trained to perform a match-to-sample discrimination task; effects of repeated sublethal exposure to the organophosphate nerve gas, soman, upon task performance were then explored. Both acute and subchronic exposure schedules were employed, and soman potency was verified by assay of soman-induced inhibition of acetylcholinesterase activity in whole blood, plasma, and erythrocytes. A characteristic profile of behavioral effects encompassing immediate, persistent, and delayed effects was observed. Immediate dose-related effects of soman included: increases in mean session response time, increases in errors, and decreases in extra responses. Seizures were also observed at the highest dose of soman employed (5 micrograms/kg). The increase in mean session response time was due to intermittent lapses in responding to stimuli (attentional deficits). Both the attentional deficits and intermittent generalized seizures were also persistent effects, with both occurring randomly after acute exposure to 5 micrograms/kg soman. Preliminary evidence suggests that occurrence of attentional deficits was associated with the occurrence of generalized and/or focal seizures; and that these effects may reflect irreversible lesions which become more threatening to the animal with increasing time. An additional, delayed effect was a sudden marked increase in the incidence of extra inconsequential responses which occurred several weeks after cessation of soman exposures.
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PMID:Neurobehavioral effects of repeated sublethal soman in primates. 408 Jul 70

507 Holtzman rats received injections, through chemitrodes chronically implanted into the basolateral amygdala, of 0.2-1 microliter of sterile isotonic solution containing nanomolar quantities of cholinergic muscarinic agonists and/or antagonists. The bulk of the injected solution diffused only a short distance as judged by autoradiography. Once daily injections of 2.7 nmoles of carbamylcholine, an initially subconvulsive dose, kindled the progressive development of epileptic seizures similar to those seen in electrical amygdaloid kindling. This response was dependent on dose and on interstimulus interval, and once established persisted at least 8 weeks without further stimulation. Spontaneous seizures were observed in some fully kindled animals. No kindling-specific changes were seen by light microscopy. Muscarine (3 nmol) and the active (+), but not the inactive (-), isomer of acetyl-beta-methylcholine also kindled seizures. The action of (+)-acetyl-beta-methylcholine was potentiated by the cholinesterase inhibitor physostigmine. The muscarinic antagonists atropine and quinuclidinyl benzylate (QNB) blocked kindling by carbamylcholine or muscarine. Atropine, QBN and scopolamine greatly reduced agonist-induced seizures in previously kindled rats. Highly significant transfer effects were observed between muscarinic agonists, i.e. muscarine-kindled rats had widespread seizures on their first carbamylcholine exposure and vice versa. Kindled animals had a lowered seizure threshold for muscarinic agonists. Dibutyryl cyclic GMP produced seizures but no kindling. Those results demonstrate that in this model the stimulation of a group of muscarinic cholinergic synapses is both necessary and sufficient to induce a kindled state characterized by both evoked and spontaneous seizures, and support the view that epilepsy can be acquired and expressed transsynaptically.
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PMID:Chemical kindling by muscarinic amygdaloid stimulation in the rat. 661 79

The (14C)-2-deoxyglucose procedure was used to determine the effects of the potent acetylcholinesterase inhibitor Soman on regional metabolism in the brain. Groups of rats were given 112 micrograms/kg Soman, 84 micrograms/kg Soman, or saline i.m., and 15 min later the (14C)-2-deoxyglucose mapping procedure was initiated. All animals given 112 micrograms/kg Soman and 2 of 6 given 84 micrograms/kg Soman developed seizures that continued throughout the mapping procedure. Very high rates of glucose use occurred in most of the brain regions studied during seizures. The most striking increases occurred in substantia nigra, septum, outer layer of dentate gyrus of the hippocampus, hippocampal body, frontal cortex, caudate, ventral thalamus, parietal cortex, medial geniculate and interpeduncular nucleus. Only the inferior colliculus, superior olivary nucleus and lateral habenula were unaffected by the seizures. The mid layers of cerebral cortex rostral to superior colliculus showed marked reductions in glucose use which may represent inhibition of neuronal activity or functional failure from depleted energy reserves. The animals given 84 micrograms/kg i.m. that did not have seizures had regional glucose use patterns similar to the controls. The results indicate that the brain damage observed by others in Soman treated rats may be in part due to the excessive neuronal stimulation that occurs during the prolonged Soman-induced seizure.
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PMID:Brain regional glucose use during Soman-induced seizures. 668 61

Distinctive acute brain damage involving limbic and related brain regions develops in adult rats following sustained limbic seizures induced by systemic administration of kainic acid or dipiperidinoethane (DPE) or by intra-amygdaloid injection of kainic acid or folic acid. This seizure-brain damage (S-BD) syndrome is of particular interest because it tends to parallel the type of seizures and brain damage seen in human temporal lobe epilepsy. We have observed that DPE induces the S-BD syndrome by systemic but not intra-mygdaloid injection, whereas an oxidized DPE derivative which structurally resembles the cholinergic agonist oxotremorine is effective when injected into the amygdala. Prompted by this finding, we injected known acetylcholine (ACh) agonists and cholinesterase (ChE) inhibitors into the rat amygdala and found that either class of agent reproduces this type of S-BD syndrome. These and related findings suggest that ACh mechanisms might have a more important role in human epilepsy and epileptic brain damage than has generally been appreciated.
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PMID:Seizure-related brain damage induced by cholinergic agents. 682 30

Anticholinesterase insecticides can be lethal, especially to small children. Prevention, not treatment, is the key to lowering the mortality rate. However, treatment, when necessary, can be effective if the poisoning agent is identified quickly as an anticholinesterase insecticide and therapy is begun immediately and aggressively. Large doses (up to 5 gm) of atropine, which block the parasympathetic effects of the poison, in conjunction with pralidoxime, a cholinesterase regenerator, need to be administered, second only in priority to establishing an airway. The second line of attack after adequate atropinization is supportive. Assistance with ventilation is individualized according to the degree of patient need. Intake with cautiously vigorous fluid therapy and output via Foley catheter are essential. Gastric lavage, seizure precautions and control as necessary, good body hygiene, and frequent turning are also part of necessary nursing intervention. Prognosis is fairly good if improvement is shown after therapy is begun. Maintaining adequate atropinization seems to be difficult yet essential to the success of the treatment and a good prognosis for the patient.
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PMID:Anticholinesterase insecticide poisoning. 692 Nov 96

Injection of a few nanomoles of the muscarinic agonists carbamylcholine, muscarine or (+)-acetyl-beta-methylcholine once a day into the rat amygdala was initially subconvulsive, but on repetition led to the progressive development of kindled epileptic seizures. This behaviour was stereospecific, was potentiated by the cholinesterase inhibitor physostigmine, and was blocked by the muscarinic antagonists atropine, QNB and scopolamine. The kindling potencies of cholinergic muscarinic agonists and antagonists paralleled their relative affinities for muscarinic receptors in vitro. No changes in muscarinic receptors, in cholinesterase or in choline acetyltransferase were observed in kindled brains after a stimulation-free period of at least 1 week. These data support the aggregate hypothesis of epileptogenesis and suggest that abnormal activity through a particular group of muscarinic synapses can be sufficient to generate an epileptic focus.
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PMID:Kindling: a pharmacological approach. 696 22


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