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

This study investigated the ability of hyperbaric exposure to antagonize ethanol's anticonvulsant effect on isoniazid (INH)-induced seizures. Drug-naive, male C57BL/6 mice were injected intraperitoneally with saline, 1.5, 2.0, or 2.5 g/kg ethanol followed immediately by an intramuscular injection of 300 mg/kg of INH. The mice were then exposed to either 1 atmosphere absolute (1 ATA) air, 1 ATA helium-oxygen gas mixture (heliox), or 12 ATA heliox at temperatures that offset the hypothermic effects of helium. Ethanol increased the latency to onset of myoclonus in a dose-dependent manner. Exposure to 12 ATA heliox antagonized ethanol's anticonvulsant effect at 2.0 and 2.5 g/kg, but not at 1.5 g/kg. Ethanol also increased the latency to onset of clonus in a dose-dependent manner beginning at 2.0 g/kg. Exposure to 12 ATA heliox antagonized this anticonvulsant effect. When exposed to 12 ATA heliox, the blood ethanol concentrations at time to onset of myoclonus were significantly higher in mice treated with 2.5 g/kg of ethanol as compared with blood ethanol concentrations of mice exposed to 1 ATA air. These findings extend the acute behavioral effects of ethanol known to be antagonized by hyperbaric exposure and support the hypothesis that low-level hyperbaric exposure blocks or reverses the initial action(s) of ethanol leading to its acute behavioral effects.
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PMID:Low-level hyperbaric antagonism of ethanol's anticonvulsant property in C57BL/6J mice. 784 5

Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of gamma-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O2 exposure at an inspired O2 fraction of 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elimination of glutathione-induced protection from hyperbaric hyperoxia by acivicin. 791 99

The neurophysiological effects of the novel anticonvulsant lamotrigine on the high pressure neurological syndrome, HPNS, were investigated in the rat and nonhuman primate Papio anubis. Rats were exposed to pressure at a rate of 3 ATA per min in a helium/oxygen environment. They were pretreated with either lamotrigine isethionate 15, 30, or 60 mg/kg IP or control vehicle. After 15 and 30 mg/kg there were no changes in onset pressures for any of the grades of tremor or myoclonus. After 60 mg/kg, tremor was much slower, at 7-9 Hz, than the 15-20 Hz seen in controls. Four baboons were exposed to pressure at 0.33 ATA per min in the same environment and treated with lamotrigine isethionate at 7.5 mg/kg/h i.v. Each animal underwent a control and a drug-treated exposure. No changes in the onset or severity of HPNS behavioural signs were observed. However, an increase in alpha wave amplitude of the EEG was almost prevented. In both species sustained myoclonic jerking occurred at pressures similar to those at which seizure activity was observed in control exposures. It is concluded that although lamotrigine is protective in several models of neuronal excitation, it is ineffective in protecting against behavioural signs associated with high atmospheric pressure.
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PMID:Lack of effect of lamotrigine against HPNS in rodent and primate models. 791 27

The neurophysiological effects of 2 novel AMPA/kainate receptor antagonists, GYKI 52466 and LY 293558, on the high pressure neurological syndrome have been investigated in the rat and baboon (GYKI 52466) and rat (LY 293558). Rats were exposed to increasing ambient pressures of helium and oxygen at 3 ATA/min, on one occasion each. GYKI 52466 at 20 mumol/kg i.v. immediately before, followed by 70 mumol/kg/hr i.v. during compression delayed tremor by 85% and myoclonus by 30%, compared with control vehicle, and no side effects were observed. Seizure activity was not affected by any of the doses used. LY 293558 at 36 mumol/kg i.p. delayed tremor and myoclonus (44% and 12%), LY 293558 72 mumol/kg additionally delayed seizure activity (21%). Side effects, principally tranquilization at the higher dose, were also noted. Six baboons were exposed to a maximum pressure of 91 ATA at 0.3 ATA/min, in the same environment, on two occasions. One exposure was treated with an i.v. infusion of GYKI 52466 15.2 mumol/kg/hr, the other with the same volume of control vehicle. Limb and face tremor and myoclonus were delayed and the severity of signs reduced. No seizures were observed in the drug treated group before 91 ATA. EEG changes associated with exposure to pressure were not affected. It is concluded that antagonism at the AMPA/kainate receptor by GYKI 52466 and LY 293558 beneficially alters HPNS signs but in a manner which is dependent on both the drug and species being studied.
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PMID:Protection from high pressure induced hyperexcitability by the AMPA/kainate receptor antagonists GYKI 52466 and LY 293558. 793 94

CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
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PMID:Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. 846 4

Age is a natural factor that has been found to significantly affect sensitivity to hyperbaric hyperoxia (HBO). Exposure to HBO may lead to damages in the energy metabolism of the brain cells. The aim of this study was to test the effect of HBO on the metabolic, hemodynamic and electrical activities in the newborn dog. The study was performed using one-day- to 70-day-old puppies. The puppies were placed in a pressure chamber. The pressure of pure O2 in the chamber was raised by 5 atmospheres (ATA, 75 psi = 6 ATA) within 10 min. The first biochemical change to take place during HBO was oxidation of mitochondrial NADH. The age of the puppy was found to affect the time to the initiation of seizures. In the puppies under the age of 24 days, the average time was 35.1 +/- 5.9 min. In the puppies of 24 days old and older, the average time was 5.1 +/- 0.8 min. In the younger puppies, there was a later occurrence of blood vessel contractions and a longer life span compared to the older puppies. The comparison between the puppies of different ages during exposure to HBO showed differences in the metabolic response, hemodynamic changes and electrical activity. These differences can partially explain the higher resistance in the younger puppies to HBO.
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PMID:The effect of hyperbaric hyperoxia on brain function in the newborn dog in vivo. 1087 91

The purpose of the present study was to explore the relation between the modulation of cerebral blood flow and the latency of hyperbaric oxygen-induced convulsion. There were two parts in this study. First, the effect of acetazolamide on the latency of hyperbaric oxygen-induced convulsion was observed. 32 Sprague-Dawley (SD) rats were randomly divided into four groups: the acetazolamide 200, 20, 2 mg/kg body weight and normal saline (NS) group. The animals were given intraperitoneally acetazolamide or NS, respectively, before being exposed to the pressure of 6 ATA (absolute atmosphere) of pure oxygen. The time from exposure to the onset of seizure (clonic-tonic convulsion) was recorded for each animal according to behavioral observation. Second, the changes in maleic dialdehyde (MDA) and the activity of glutathione peroxidase (GSH-PX) were measured after acetazolamide treatment. 40 SD rats were randomly divided into five groups: NS group, 6 min with NS group, 6 min with acetazolamide group, 16 min with NS group, and 16 min with acetazolamide group. The dose of acetazolamide was 20 mg/kg body weight. After injection of NS or acetazolamide, the animals were subjected to the pressure of 6 ATA of pure oxygen in respect to its time course group. The rats were decapitated and the cortex, hippocampus, and striatum of brains were dissected and homogenized. The content of MDA and the activity of GSH-PX in these tissues were determined. We found that (1) there was a significant difference in the latency of hyperbaric oxygen-induced convulsion between the acetazolamide 200 mg/kg group and the NS control group, as well as between the acetazolamide 20 mg/kg group and the NS control group (P<0.01), whereas there was no significant difference between the NS group and the acetazolamide 2 mg/kg weight group (P>0.05). The latency of these groups were listed as follows: 9.78+/-1.94 min for 200 mg/kg body weight group, 10.92+/-1.68 min for 20 mg/kg body weight group, 24.32+/-4.33 min for 2 mg/kg body weight group and 22.02+/-4.32 min for NS control group. (2) there was no significant difference between all groups in the activity of GSH-PX, though it varied with the oxidation levels. In the cortex and hippocampus, the activity of GSH-PX boosted up at first, but with the progress of the oxidation it was impaired. In the striatum, the activity of GSH-PX increased stepwise with the aggravation of the oxidation. The MDA content in the cortex increased significantly in the group of 6 min with acetazolamide (P<0.01), as well as the group of 16 min with acetazolamide group both in cortex and hippocampus (P<0.01, P<0.05). The MDA content of all groups is correlated with the dose of acetazolamide and the exposure time. These results suggest that acetazolamide which dilates the brain arteriolar obviously shortens the latency of hyperbaric oxygen-induced convulsion, and that acetazolamide dilates the vessels and increases the supply of the oxygen breaking into the brain tissues and aggravates the oxidation. The hyperbaric oxygen-induced convulsion correlates closely with the oxidation injury.
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PMID:[Effect of acetazolamide on the latency of hyperbaric oxygen-induced convulsion]. 1512 24

The purpose of the present study was to explore the relation between the modulation of cerebral blood flow and the latency of hyperbaric oxygen-induced convulsion. There were two parts in this study. First, the effect of acetazolamide or (and) indomethacin on the latency of hyperbaric oxygen-induced convulsion was observed. Seventy Sprague-Dawley (SD) rats were randomly divided into 7 groups: the acetazolamide 200, 20, 10, 7.5, 5, 2.5 mg/kg body weight and normal saline (NS) group. Forty rats were divided into 5 groups: indomethacin 20, 10, 5, 2.5 mg/kg body weight and NS groups. Another 40 rats were divided into 5 groups which were administered with indomethacin in the dose of 0 mg/kg (NS), 0 mg/kg (NS), 5, 10 and 20 mg/kg body weight. Thirty min later the first group was given NS, and all the other four groups were given acetazolamide with a dose of 7.5 mg/kg body weight. The animals were given acetazolamide or (and) indomethacin intraperitoneally, and 20 min later they were exposed to the pressure of 6 ATA (absolute atmosphere) of pure oxygen. The time from exposure to the onset of seizure (clonic-tonic convulsion) was recorded for each animal according to behavioral observation. Second, the change of maleic dialdehyde (MDA) was measured after acetazolamide and (or) indomethacin treatment. Seventy-two SD rats were randomly divided into 9 groups: Control, 6 and 16 min respectively with NS, acetazolamide, indomethacin, and both acetazolamide and indomethacin group. The dose of acetazolamide was 7.5 mg/kg body weight and the dose of indomethacin was 20 mg/kg body weight. After injection of drugs, the animals were subjected to the pressure of 6 ATA of pure oxygen in respect to its time course group. Then the rats were decapitated and the cerebral cortex was dissected and homogenized. The content of MDA was determined. We found that (1) when the dose of acetazolamide is higher than 7.5 mg/kg, it shortened the latency to hyperbaric oxygen-induced convulsion significantly (P<0.05, P<0.01). There was no significant difference in the latency between every to hyperbaric oxygen-induced convulsion significantly (P<0.05, P<0.01). There was no significant difference in the latency between every two groups of rats treated with different doses of indomethacin. But when the rats were administered acetazolamide of 7.5 mg/kg body weight after being pretreated with indomethacin of 20 mg/kg body weight, the outbreak of convulsion was put off remarkably (P<0.05). (2) In comparison with the control, the content of MDA in the group treated with acetazolamide increased significantly (P<0.01), but when the rats were treated with both acetazolamide and indomethacin, the content of MDA was reduced significantly both in 6 and 16 min exposure time projects (P<0.05, P<0.01). These results suggest that acetazolamide which dilates the brain arterioles can obviously shorten the latency of hyperbaric oxygen-induced convulsion and aggravate the oxidation of the brain. Indomethacin can resist acetazolamideos effect on the latency and oxidation level when the animals were exposed to the hyperbaric oxygen. The activity of carbonic anhydrase correlates closely with the oxidation injury.
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PMID:[Influence of acetazolamide given intraperitoneally on the latency to hyperbaric oxygen-induced convulsion of rats.]. 1609 93

Intermittent air breaks during hyperbaric oxygen (HBO2) exposures protect against pulmonary and central nervous system (CNS) toxicity. The mechanisms of this beneficial effect from intermittency are not known. In this study, we examined if release of vasoconstriction during HBO2 exposure indicates a threshold for toxic dose of HBO2 and how it may be related to tolerance by intermittency. Awake rats instrumented for EEG and cerebral blood flow (CBF) measurement were exposed to 100% O2 at 6 ATA (absolute pressure). Air breaks of 3 or 10 min were given at different times after CBF increase. Following the air break, animals were exposed to 100% O2 until seizure and total O2 time was used to calculate benefit/toxicity. The most beneficial schedule was then used to assess the role of the multiple air breaks in extension of HBO2 tolerance. A significant increase in seizure latency was observed in animals with a single 3- or 10 min air break given 5-10 min after CBF increase. No change in seizure latency was observed when air breaks were given beyond (>10 and <5 min) this window. The duration of total O2 time to seizures was doubled with multiple 3 min air breaks, and quadrupled with 10 min air breaks compared with continuous HBO2 exposures. With more time spent on O2, the duration of air breaks was not sufficient for recovery from O2 toxicity and for CBF to return to baseline. Results show that an "optimal window" of HBO2 exposure is required for benefits by intermittent exposure to air.
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PMID:Extension of brain tolerance to hyperbaric O2 by intermittent air breaks is related to the time of CBF increase. 1654 46

CNS O2 toxicity is manifested most profoundly by generalized motor convulsions. The hypothesis was tested that HBO2 triggers seizures by an excitatory to inhibitory neurotransmitter imbalance produced by neuronal nitric oxide (NO) activity. Anesthetized rats were exposed to 5 ATA HBO2 for 75 min with or without prior inhibition of nNOS. Interstitial NO and amino acids: aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) were determined in the striatum by microdialysis coupled with HPLC. Blood flow and EEG in the same striatal region were measured simultaneously. Rats treated with 7-NI showed no EEG spikes of O2 toxicity, while seizure latency for untreated rats was 63 +/- 7 min. Significant increases in NO metabolites and blood flow were observed in control rats before seizures. HBO2 did not change Glu significantly and increased Asp slightly whereas GABA decreased progressively by 37 +/- 7%. Pretreatment with 7-NI led to a significantly smaller decline in GABA. Overall, the simplified excitotoxicity index Glu/GABA increased significantly after 60 min of HBO2 in control but fell in rats treated with 7-NI. We conclude that HBO2-stimulated neuronal NO production promotes an imbalance between glutamatergic and GABAergic synaptic function implicated in the genesis of oxygen-induced seizures.
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PMID:Nitric oxide amplifies the excitatory to inhibitory neurotransmitter imbalance accelerating oxygen seizures. 1686 30


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