Abstract:
The purpose of the study was to investigate the dynamics of seizure activity and
markers of neuroinflammation in kindled rats under conditions of individual and combined
use of pitolisant and pioglitazone. Under conditions of acute observation in rats kindled with
pentylenetetrazol, repeated administration (35.0 mg/kg, i.p.) of the behavioral, electrographic seizure manifestations, the density of microvessels, and the level of HIF-1α in brain structures
have been investigated. The data obtained showed that pitolisant use in previously ineffective
dosage (5,0 mg/kg, i.p.) but against the background of the administration of pioglitazone (50,0
mg/kg, i.p.) was accompanied by the anticonvulsant effect, which was expressed as
prevention of generalized tonic-clonic seizures as well as in reduction of seizure severity and
triple shortage of the ictal discharges duration in brain frontal cortex. Also, combined
administration of pitolisant (5,0 mg/kg, i.p.) and (50,0 mg/kg, i.p.) prevented kindlinginduced angiogenesis in the frontal cortex by 55,2% and the level of HIF-1α in the
hippocampal gyrus dentatus by 38,6%. Thus, complex antiepileptic effects significantly2
exceeded those observed after separate drug administration have been described. These data
support the synergistic antiepileptic action of the investigated compounds, favoring the
rationality of exploring a combination of modulators of the histaminergic system with PPAR-
γ agonists as antiseizure therapy.
