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Altered seizure susceptibility in mice deficient in the aquaporin-4 membrane water channel


, : Altered seizure susceptibility in mice deficient in the aquaporin-4 membrane water channel. Society for Neuroscience Abstracts 27(1): 914

Seizure activity is known to lead to cerebral edema, and animals deficient in the membrane water channel aquaporin-4 show decreased cerebral edema and improved neurological outcome following water intoxication or ischemic challenge. Therefore, we tested seizure susceptibility in aquaporin-4 mutant mice. Mice deficient in aquaporin-4 (-/-) or wild-type controls (+/+) were given the chemo-convulsants pentylenetetrazol (PTZ, 40 or 50 mg/kg) or kainic acid (20 mg/kg) via intraperitoneal injection and monitored for seizure activity by an observer blinded to genotype. At 40 mg/kg PTZ, all (7/7) wild-type animals exhibited seizure activity, whereas 6/7 mice deficient in aquaporin-4 (-/-) did not exhibit any seizure activity. At 50 mg/kg PTZ, both groups exhibited seizure activity. Latency to forelimb clonus was 94+-13 sec. in WT animals and 123+-10 sec. in AQP-4 -/- animals (p=.13); and latency to generalized tonic-clonic seizures was 188+-43 sec. for WT animals and 330+-51 sec. in AQP-4 -/- animals (p=.05). After KA, 5/7 WT and 4/4 -/- animals exhibited seizure activity. Latency to forelimb clonus was 38.2+-6.7 min. for WT animals and 23.0+-1.6 min. for AQP-4 -/- animals (p=.09); and latency to generalized seizure was 38.8+-6.2 min. for WT animals and 27.5+-3.7 min. for AQP-4 -/- animals (p=.19). Of note, all of the AQP-4 -/- animals exhibited sustained tonic-clonic seizure activity, and 2/4 of the AQP-4 -/- animals died from status epilepticus compared to only 1/7 of the WT animals. These preliminary results suggest that cellular volume regulation via brain water channels may modulate the expression and generalization of seizure activity.

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