Dynamics of nitrergic system activation in the rat brain provoked by experimentally induced seizures

• Published in: Neuroscience 2025-01, Vol.564, p.290-298
• Main Authors: Kantor, Szymon, Drzał, Agnieszka, Setkowicz, Zuzanna, Elas, Martyna, Janeczko, Krzysztof
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Convulsants - toxicity; Disease Models, Animal; Electron paramagnetic resonance spectroscopy; Electron Spin Resonance Spectroscopy; Epilepsy; Gasotransmission; Male; Nitric oxide; Nitric Oxide - metabolism; Pilocarpine; Rats; Rats, Wistar; Seizures; Seizures - chemically induced; Seizures - metabolism; Seizures - physiopathology
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2024.10.032

•Nitric oxide is a potent, yet unrecognised, non-classical gaseous neurotransmitter.•In the context of epilepsy, nitric oxide persists as an enigmatic subject.•The nitrergic system engages in the acute brain response to epileptic activity.•The nitrergic system activation diminishes quickly after the occurrence of seizures.•This activation may serve as an antiepileptogenic compensatory mechanism.•Under usual conditions, this activation is insufficient to attenuate seizures. Epilepsy is a pathophysiological condition displaying a highly diverse phenotype. Consequently, comprehending the mechanisms underlying seizures necessitates moving beyond a simplistic model focused on the imbalance between the classical excitatory and inhibitory neurotransmitter systems. Nitric oxide (NO), a nonclassical and multifunctional gaseous neurotransmitter, has the potential to exert a profound influence on epileptic reactivity. Unfortunately, numerous studies have not provided clear answers about its involvement in the pathophysiology of epilepsy. The objective of our study was to delineate the temporal dynamics of alterations in nitrergic system activation after experimentally induced seizures. Seizures were induced in 2-month-old male Wistar rats (n = 55) by an administration of pilocarpine. Over a 6-hour observation period, seizure behaviour intensity was continuously evaluated using a modified Racine scale. At intervals of 6, 12, 24, 48, or 96 h post-chemoconvulsant administration, NO spin trapping was conducted with ferrous-diethyldithiocarbamate complexes (Fe(DETC)2). Electron paramagnetic resonance (EPR) spectroscopy was employed to quantify mononitrosyl iron complexes (NO-Fe(DETC)2) in the brain. The temporal kinetic of NO release after seizures revealed a rise in NO synthesis during the initial 12 h. Subsequently, a sharp decline occurred, returning to baseline 96 h after pilocarpine injection. Notably, our research suggests that the level of NO synthesis does not interfere with the severity of the epileptic seizures that occur. In light of this, we propose that the nitrergic system is quickly activated in the epileptic brain as a compensatory mechanism of the central nervous system. However, under usual conditions, this activation is insufficient to effectively attenuate seizures.