Epilepsy Research 184 (2022) 106972 Available online 26 June 2022 0920-1211/© 2022 Elsevier B.V. All rights reserved. Relation between orexin A and epileptic seizures Gokce Ayhan Arslan a, 1, 2, * , Serap Saygi a , Ebru Bodur b , Cigdem Cicek c , F. Irsel Tezer a, 1 a Hacettepe University Faculty of Medicine, Department of Neurology, Ankara, Turkey b Hacettepe University Faculty of Medicine, Department of Biochemistry, Ankara, Turkey c Yuksek Ihtisas University Faculty of Medicine, Department of Biochemistry, Ankara, Turkey A R T I C L E INFO Keywords: Orexin Epilepsy Seizure Sleep Human orexin Serum orexin ABSTRACT Introduction: One of the unknown mechanisms in epilepsy pathogenesis is the involvement of the hypothalamic neuropeptide orexin. Although the relationship between orexin and sleep has been revealed, its effect in epilepsy has not been fully clarifed. In this study, we aimed to show the relationship between orexin A and the seizures that occur during sleep and wakefulness. Material and methods: This study included 40 patients with drug-resistant focal epilepsy and 37 healthy controls. Night basal orexin (NBO) and morning basal orexin (MBO) levels were measured using enzyme-linked immu- nosorbent assay in patients and controls. Serum samples were collected from patients after epileptic seizures during sleep and wakefulness. Results: In both patients and controls, MBO levels (median: 1039 pg/mL, interquartile ranges [IQR] (899–1078)) were higher than NBO levels (median 989 pq/mL, IQR (893–1078) (p = 0.02). Basal orexin levels were lower in patients than in controls (p < 0.001). However, while the duration of seizures was shortened in awake seizures, the level of orexin increased (p = 0.007). Additionally, orexin levels after nocturnal seizure were higher in patients who had an ictal electroencephalography onset in the left hemisphere or a lesion in the left temporal lobe (p = 0.02; p = 0.01, respectively). There was no relationship between postictal somnolence and orexin levels. Although there was no signifcant difference, the level of post-seizure orexin increased compared to the basal values, especially in seizures during sleep. Discussion: The increase in serum orexin levels, especially after seizures, suggests that orexin may be associated with the epileptogenic effect. In further studies, determination of orexin from cerebrospinal fuid (CSF) and correlation of CSF and serum orexin levels may provide more useful information regarding the relationship between orexin and epilepsy. 1. Introduction The underlying mechanism of epileptic seizures remains controver- sial. Recently, there has been increasing interest in the relationship between orexin and epilepsy (Ng, 2017). Orexin, also known as hypo- cretin, is a hypothalamic neuropeptide involved in wakefulness and behavioral arousal. It also plays a special role in the regulation of sleep. Orexinergic neurons maintain wakefulness by projecting to wake-promoting areas with infuences on the monoaminergic and cholinergic systems (Scammell, 2015; Schwartz and Kilduff, 2015). Orexin activity is selectively highest during waking, whereas it de- creases in slow-wave sleep and is completely absent in rapid eye movement (REM) sleep (Schwartz and Kilduff, 2015; Tsujino and Sakurai, 2009). Strong orexinergic tone stimulates wakefulness with mild cortical desynchronization, weak orexinergic tone stimulates slow-wave sleep with strong thalamocortical synchronization, and orexin phasic bursts stimulate hypersynchronized state transitions (Ng, 2017). Moreover, orexinergic neurons lead to suppression of REM sleep Abbreviations: REM, rapid eye movement; EEG, Electroencephalography; PSG, Polysomnography; s, second; MRI, Magnetic resonance imaging; mL, milliliter; min, minute; NBO, night basal orexin; MBO, morning basal orexin; SRO, seizure related orexin; NREM, nonrapid eye movement; HCRT1, The human orexin A (hypocretin- 1); ELISA, enzyme-linked immunosorbent assay; pg, pictogram; IQR, interquartile range; CSF, cerebrospinal fuid; AED, antiepileptic drug. * Correspondence to: Hacettepe University Medicine Faculty, Department of Neurology, Sihhiye, 06230 Ankara, Turkey. E-mail addresses: gokce_ayhan@yahoo.com.tr (G.A. Arslan), ssaygi@hacettepe.edu.tr (S. Saygi), bodurebru@yahoo.com (E. Bodur), cigdemcicek66@gmail.com (C. Cicek), irseltezer@yahoo.com.tr (F.I. Tezer). 1 These authors are equally contributed 2 Orcid: 0000–0002-1099–3443 Contents lists available at ScienceDirect Epilepsy Research journal homepage: www.elsevier.com/locate/epilepsyres https://doi.org/10.1016/j.eplepsyres.2022.106972 Received 7 September 2021; Received in revised form 23 February 2022; Accepted 22 June 2022