Modulatory effects of delta sleep-inducing peptide in a lindane model of generalized seizures

Dragan Hrnčić, Željko Grubač, Nikola Šutulović, Aleksandra Rašić-Marković, Anida Ademović, Olivera Stanojlović


Paper description:

  • Efficient drug treatment for resistant forms of epilepsy still haven’t been found. Lindane-induced seizures are refractory to numerous classical antiepileptic drugs. Delta sleep inducing peptide (DSIP) is a neuroprotective nonapeptide capable of optimizing the excitation/inhibition relationship.
  • It is not known whether DSIP is capable of modulating refractory seizures. In our work we demonstrated by behavioral and electroencephalographic studies that DSIP can beneficially modulate the severity of lindane-induced seizures and ictal period frequency.
  • DSIP has the potential to be an add-on component in antiepileptic treatment strategy for refractory seizures.

Abstract: Delta sleep-inducing peptide (DSIP) is an endogenous peptide that is constantly present in several different brain regions. Lindane is used as a pesticide and scabicide, but it also induces seizures refractory to conventional antiepileptics. The aim of this paper was to determine whether DSIP modulates lindane-induced seizures in rats in a behavioral and electroencephalographic (EEG) study. DSIP (1 mg/kg, i.p.) or dimethyl-sulfoxide (DMSO, 0.5 ml/kg, intraperitoneally (i.p.)) were injected 30 min before lindane (8 mg/kg, i.p.) to adult male rats with previously implanted electrodes for EEG registration. During the following 30 min, the EEG was registered, and the following behavioral characteristics of seizures were observed: incidence, latency and intensity. A descriptive scale with grades from 0 to 4 provided an estimate of seizure intensity. In the EEG, the number and duration of ictal periods were analyzed using NeuroSciLaBG (Belgrade, Serbia) software. The lethality rate was also analyzed. DSIP-treated animals showed significantly modified characteristics of lindane-induced seizures when compared to the group without DSIP pretreatment (i.e. a reduced seizure intensity and a prolonged seizure latency period). However, no significant effects of DSIP on seizure incidence and lindane-induced lethality were observed. EEG analyses showed a significantly decreased number of lindane-induced EEG ictal periods in DSIP-treated animals, but with unaltered duration. These results show that DSIP favorably modulates lindane-induced seizures in rats, showing a potential to be an adjuvant component of antiepileptic treatment strategy for refractory seizures.

Received: January 9, 2018; Revised: February 7, 2018; Accepted: March 30, 2018; Published online: April 19, 2018

How to cite this article: Hrnčić D, Grubač Ž, Šutulović N, Rašić-Marković A, Ademović A, Stanojlović O. Modulatory effects of delta sleep-inducing peptide in a lindane model of generalized seizures. Arch Biol Sci. 2018;70(3):…


behavior; delta sleep-inducing peptide (DSIP); EEG; epilepsy; refractory seizures lindane

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