Anticonvulsant and neuronal protective effects of propofol on experimental status epilepticus

Propofol (2,6-diisopropylphenol) is an intravenous (i.v.) short-acting agent frequently used in neuroanesthesia and recently successfully used to treat refractory status epilepticus (SE). Conversely, there are over 50 reported cases of epileptic seizures following propofol-induced anesthesia, suggesting that propofol may aggravate seizures, especially in seizure-prone patients. The aim of this study is to assess the clinical and histologic effects of propofol on experimental SE. Status epilepticus was induced In adult rats by kainic acid [KA, 20 mg/kg, intraperitoneal (i.p.)]; in this model there is a time interval between KA administration and SE onset. To assess the effects of propofol on seizure-prone rats, propofol was given 15 minutes after the injection of KA before onset of seizures (group I, N = 12; 15 mg/kg i.v.). To assess the effects of propofol as an anticonvulsant, it was given 15 minutes after onset of SE to other rats (group II, N = 8; 15 mg/kg/i.v.). Control rats were injected with saline in both groups (group I N = 5; group II N = 5). Histology and immunohistochemistry were used to assess seizure-induced hippocampal cellular damage 2 weeks after SE. In group I rats, seizure latency was as not different from controls. Furthermore, SE occurred less frequently in propofol pretreated rats than controls (p < .05). In group II rats, propofol broke SE in all treated rats. Furthermore, it reduced SE-induced mortality rate (p < .05). Finally, propofol had neuronal protective effects on hippocampal neurons. This resulted in decreased seizure-induced neuronal loss and astrocytosis in propofol-treated animals compared to controls. This study shows that propofol is not proconvulsant. Furthermore, propofol aborts kainate-induced SE and offers protection from seizure-induced hippocampal neuronal damage. (C) 1998 by Elsevier Science Inc. All rights reserved.