Abstract
Mice deficient in the glial water channel aquaporin-4 (AQP4) show decreased cerebral edema and improved neurological outcome following water intoxication or ischemic challenge. In this report, we tested seizure susceptibility in AQP4 mice. AQP4 mice and wild-type controls were given the chemoconvulsant pentylenetetrazol (PTZ) and monitored for seizure activity. At 40 mg/kg PTZ, all wild-type mice exhibited seizure activity, whereas six of seven AQP4 mice did not exhibit seizure activity. At 50 mg/kg PTZ, both groups exhibited seizure activity; however, the latency to generalized (tonic-clonic) seizures was significantly lower in wild-type than AQP4 mice. These results suggest that glial water channels may modulate brain excitability and the initiation and generalization of seizure activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / genetics
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Animals
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Aquaporin 4
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Aquaporins / deficiency*
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Aquaporins / genetics
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Brain / drug effects
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Brain / metabolism*
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Brain / physiopathology
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Brain Edema / genetics
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Brain Edema / metabolism
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Brain Edema / physiopathology
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Convulsants / pharmacology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Electroencephalography
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Epilepsy / chemically induced
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Epilepsy / genetics*
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Epilepsy / metabolism
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Genetic Predisposition to Disease / genetics*
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Mice
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Mice, Knockout
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Neurons / drug effects
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Neurons / metabolism
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Pentylenetetrazole / pharmacology
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Reaction Time / drug effects
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Reaction Time / genetics*
Substances
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Aqp4 protein, mouse
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Aquaporin 4
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Aquaporins
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Convulsants
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Pentylenetetrazole