Gaye Boztepe Yılmaz, Kemal Tolga Saraçoğlu, Uğur Aykın, Metehan Akça, Cumaali Demirtaş, Ayten Saraçoğlu, Mehmet Yıldırım
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引用次数: 0
Abstract
Refractory status epilepticus (RSE) is a condition with serious mortality and morbidity rate, resistant to benzodiazepine and second-line antiepileptic drugs. This study aimed to electrophysiologically investigate the combination of NMDA receptor antagonist ketamine and GABAergic agent propofol in an RSE model induced by lithium-pilocarpine in male Sprague–Dawley rats. Seventy-two male Sprague–Dawley rats were divided into nine groups. The RSE model was induced by subcutaneous injection of lithium-CI (5 mEq/kg) and intraperitoneal injection of pilocarpine-HCl (320 mg/kg), after implanting tripolar EEG electrode. Ketamine (30, 60, and 90 mg/kg), propofol (20, 40, and 80 mg/kg), and combinations of both drugs (15 + 20 and 30 + 40 mg/kg) were administered intraperitoneally to animals with RSE. Video-EEG recordings were taken after inducing model and 48 h later. The efficacy of drugs was statistically evaluated based on spike frequencies (spikes/min) and amplitudes (mV). Compared to RSE group, it was determined that 30 and 60 mg/kg doses of ketamine provided effective seizure control and prevented mortality (p < 0.001), while the 90 mg/kg showed toxic effects in all animals and caused mortality. The 80 mg/kg dose of propofol provided seizure control and reduced the mortality rate to 16.7% (p < 0.001), whereas the 20 mg/kg resulted in a 100% mortality rate. The low-dose ketamine+propofol (15 + 20 mg/kg) combination provided early onset seizure control and were as effective as 80 mg/kg propofol (p < 0.05). The study concluded that in the experimental RSE model, seizure control could be achieved with low-dose combination of ketamine and propofol without the need for high doses as in monotherapy, thus preventing dose-related adverse effects.
期刊介绍:
The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology.
The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.