15th European Epilepsy Congress, Rome, İtalya, 7 - 11 Eylül 2024, cilt.65, sa.1, ss.117, (Özet Bildiri)
Purpose: Orexin, primarily generated by neurons in the lateral hypothalamus, serves as a neuropeptide neurotransmitter that predominantly modulates the sleep/wake cycle. Besides its established role in regulating the sleep cycle, recent findings indicate the potential involvement of the orexin system in epilepsy (Ng, M. C. Sleep 2017;40(3): zsw061). Limited data exists on role of orexins in absence seizures. There are two types of orexin types in the brain: orexin-A and orexin-B. In this research, we investigated the influence of orexin-B injections into the right lateral ventricle (ICV) on spike-and-wave discharges (SWDs) in genetically absent epilepsy rats from Strasbourg (GAERS).
Method: Under ketamine-xylazine (100 mg/kg, 10 mg/kg; ip) anaesthesia, unilateral ICV guide-cannulas and electroencephalography (EEG) recording electrodes were stereotaxically inserted into the skulls of male GAERS weighing between 200–350g. Following a recovery period, baseline EEG recordings were collected from the animals during a 3-h. The subsequent day, orexin-B doses were administered through the guide-cannulas: 0.1-nmol/5uL (n = 5), 1-nmol/5uL (n = 6), or 10-nmol/5uL (n = 7) for each group. EEG signals were captured using the Powerlab-8S system and subsequently analysed with LabChart-8.0. Statistical analysis utilized one-way Anova (p < 0.05 considered significant).
Results: The injection of 10-nmol/5uL orexin-B decreased cumulative SWDs duration compared to baseline recordings from 3648.66 ± 172.58 to 2612.99 ± 1473.21 seconds in GAERS (p = 0.02). However, other doses of orexin-B injection did not affect on the cumulative SWDs duration compared to baseline significantly.
Conclusion: Our study is the first to demonstrate the impact of orexin-B on absence epilepsy seizures. The indicated decrease in cumulative SWD following the administration of 10 nmol orexin-B suggests a potential role of the orexinergic system in absence epilepsy. In order to understand comprehensively, our ongoing study plans to evaluate the impact of higher doses of orexin-B and conduct histological assessments.