Modulation of Epileptic Activity in Rats: Focus on Sleep, Physical Exercise and Nitric Oxide–mediated Neurotransmission in a Model of Homocysteine Thiolactone–induced Seizures

Epilepsy is a chronic neurological disorder characterised by recurrent epileptic seizures. Understanding the mechanisms by which it initiates and develops, as well as its modulating factors, are of great scientific interest. Experimental models of epilepsy are useful for understanding these mechanisms. Homocysteine, an amino acid endogenously generated in the body, together with its reactive metabolite, homocysteine thiolactone (HCT), is recognised as a risk factor for a variety of diseases. HCT-induced seizures are a model of generalised epilepsy in which the coexistence of two types of epileptic activity has been documented. Th e complex interplay between sleep and epilepsy is still only poorly understood. Additionally, the relationship between physical exercise and epilepsy is quite intriguing, especially the mechanism underlying this relationship. Th e role of nitric oxide (NO)-mediated neurotransmission in the development of epileptic activity is highly debated in the existing scientific literature . In this review article, we described the modulation of epileptic activity in rats and focused on sleep, physical activity and NO-mediated signalling. First, we explain the characteristics of the experimental models of epileptic activity and the unique features of HCT-induced seizures. Second, the modulating eff ects of sleep and regular physical exercise training on epileptic activity, along with works from the authors, are discussed. Finally, the anticonvulsive eff ects of NO that is produced via nNOS and iNOS in HCT-induced seizures are reviewed. Epilepsija je hronično neurološko oboljenje koje karakteriše rekurentna pojava epileptičnih napada. Razumevanje menahizama nastanka i širenja epileptične aktivnosti, kao i foktora modulacije ovih procesa, od izuzetnog je naučnostručnog značaja. Eksperimentalni modeli epilepsije su značajni za razumevanje upravo ovih mehanizama. Homocistein, aminokiselina koja se endogeno sintetiše u organizmu, zajedno sa svojim reaktivnim metabolitom homocistein tiolaktonom (HCT), je prepoznat kao faktor rizika za nastanak različitih bolesti. Epilepsije izazvane HCT-om predstavljaju model generalizovane epileptične aktivnosti u kome je pokazana koegzistencija dva tipa napada. Složeni uzajamni odnos između spavanja i epilepsije još uvek nije dovoljno razjašnjen. Takođe, međuodnos fizičke aktivnosti i epilepsije je krajnje interesantan, naročito mehanizmi ovih odnosa. Uloga neurotransmisije posredovane azot monoksidom (NO) u nast