Experimental
Anticonvulsant and Neuronal Protective Effects of Propofol on Experimental Status Epilepticus

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Abstract

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 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.

Section snippets

Animals

The experimental procedures were conducted in 30 adult Sprague-Dawley rats (body weight: 250–500 g; Taconic Farms, NY, USA). All animals were maintained on a 12-hour light–dark cycle with an average room temperature of 23°C, humidity of 55%, and food and water ad lib. Experiments were conducted according to our Institutional Animal Care and Use Committee (IACUC) and Center for Laboratory Animal Science (CLAS) guidelines and approved protocols.

Surgery for Insertion of Intravenous Catheter

Rats were anesthetized with chloral hydrate (.3

Results

In group I rats (pretreatment), the latency to seizure onset in propofol-treated rats was not different from controls. Seizures occurred 65 ± 6 minutes after injection of KA in propofol-treated rats and 78 ± 12 minutes in controls. Furthermore, seizure severity was not worsened by propofol pretreatment. Additionally, propofol-treated rats had a lower rate of SE than controls: SE occurred in four of five control rats and only three of 12 of experimental animals (Fig. 1).

In group II rats

Discussion

Medically refractory SE causes irreversible neuronal damage and is potentially life-threatening 3, 26, 27. Therefore, new drugs are currently sought for its treatment 6, 7. Propofol, a hypnotic anesthetic agent, has met wide favor in anesthesia practice since its introduction in 1981 [28]. Its fast-acting properties including a distribution half-life of 2–4 minutes and quick metabolic clearance of 30–60 minutes, make it particularly desirable, as it allows patients to recover promptly even

Acknowledgements

This work was partially presented at the American Epilepsy Society, 1995 Annual Meeting.

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