Effect of hyperbaric oxygen on GABA transport in rat brain synaptosomes

Wheeler, D. D.; Blackburn, John G.; Tai, John Jen

doi:10.1007/bf01245116

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…Hyperbaric oxygen can also induce seizures, which has been ascribed to inhibited transport and presynaptic depletion of GABA [63]. In keeping with this explanation, such seizures can be inhibited with GABA A receptor agonists [64].…”

Section: Interaction Of Disulfiram With Hyperbaric Oxygenmentioning

confidence: 61%

Combination treatment of epilepsy with ketogenic diet and concurrent pharmacological inhibition of cytochrome P450 2E1

Palmer

2013

Medical Hypotheses

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While most epileptic patients respond to treatment with existing antiepileptic drugs, there remains a considerable number of patients in whom these drugs do not suffice. Such patients, particularly children, are often treated using the ketogenic diet. This diet imposes a strict limit on carbohydrates; while providing for adequate protein, most of the calories are supplied as triacylglycerol, much of which is metabolized to ketone bodies.Animal experiments have provided evidence that the anticonvulsant effect of the ketogenic diet is mediated by acetone and correlates with acetone levels. Acetone can be converted in vivo to glucose via acetol and pyruvate; the initial conversion to acetol is catalyzed by cytochrome P450 2E1 (CYP2E1). When CYP2E1 knockout mice are subjected to starvation to induce ketogenesis, they develop blood acetone levels much higher than those observed in wild-type mice. Similarly, pharmacological inhibition of CYP2E1 significantly increases blood acetone levels in rat and man.Taken together, these observations suggest that pharmacological inhibition of CYP2E1 has the potential to significantly increase the antiepileptic effect of the ketogenic diet. With patients that respond insufficiently to the diet alone, increased acetone levels may improve response. With patients who respond sufficiently to the diet, CYP2E1 inhibitors might allow relaxation of the fairly severe diet regimen and so improve compliance and quality of life.An existing inhibitor of CYP2E1 is the drug disulfiram. This drug also inhibits the enzyme aldehyde dehydrogenase, which functions in alcohol degradation, and in this capacity has long been used in the treatment of alcohol addiction. Disulfiram inhibits CYP2E1 at conventional therapeutic dosages and increases blood acetone levels in humans and animals. It should therefore be a viable candidate for the proposed drug/diet combination treatment.2

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Section: Interaction Of Disulfiram With Hyperbaric Oxygenmentioning

confidence: 61%

Combination treatment of epilepsy with ketogenic diet and concurrent pharmacological inhibition of cytochrome P450 2E1

Palmer

2013

Medical Hypotheses

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Effect of hyperbaric oxygen on 2-deoxy-d-glucose andl-glutamate transport in rat cortical synaptosomes

Wheeler

Blackburn

1984

Neurochem Res

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Initial velocities of uptake of L-glutamic acid and 2-deoxy-D-glucose (2-Dg) have been measured in cortical synaptosomes from rats which had been exposed to oxygen at high pressure (OHP) and compared to similar measurements in normobaric controls. Exposure to OHP had no significant effect on glutamate uptake at any combination of sodium and glutamate used. In contrast, OHP reduced 2-Dg uptake by an average of 17.5%. Although Kt was little affected, OHP exposure reduced apparent maximal transport capacity by 15%. Since hyperbaria with normal pO2 had no significant effect on uptake, the effect of OHP is an oxygen effect, rather than a pressure effect. The effects of OHP on uptake do not parallel the effects of age; glutamate transport capacity was reduced in aged animals, while 2-Dg transport was unaffected.

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Effects in vitro of l-glutamate and kainic acid on the ATPase activities of synaptosomal membranes from different areas of rat brain

Szkudlarek¹,

Lachowicz²,

R³

1986

Neuroscience Letters

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Effect of hyperbaric oxygen on GABA transport in rat brain synaptosomes

Cited by 3 publications

References 32 publications

Combination treatment of epilepsy with ketogenic diet and concurrent pharmacological inhibition of cytochrome P450 2E1

Combination treatment of epilepsy with ketogenic diet and concurrent pharmacological inhibition of cytochrome P450 2E1

Effect of hyperbaric oxygen on 2-deoxy-d-glucose andl-glutamate transport in rat cortical synaptosomes

Effects in vitro of l-glutamate and kainic acid on the ATPase activities of synaptosomal membranes from different areas of rat brain

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