Levetiracetam effect and electrophysiological mechanism of action in rats with cobalt-induced chronic epilepsy.

Levetiracetam was initially developed as a nootropic drug, although since 2002 it has been used as anticonvulsant for the treatment of partial and generalized epilepsy syndromes. The purpose of the research was to investigate anti-paroxysmal activity of levetiracetam (LEV) on the model of cobalt-induced chronic epilepsy caused by the application of cobalt to the sensorimotor area of the rat cortex to evaluate LEV impact on the different stages of epileptogenesis. LEV effects were studied at the initial stage of the epileptogenesis (2nd day after the cobalt application) and at the stage of generalized paroxysmal activity (6th day after the cobalt application). The research showed that levetiracetam administration (dosages 50 mg/kg and 200 mg/kg) at the early stage of the epileptogenesis had no statistically significant effect on the development of paroxysmal activity in both primary and secondary epileptic areas: in the ipsi- and contralateral cortex, hypothalamus and hippocampus. LEV administration on 6th day (dosage 50 mg/kg) did not have statistical effect on the epileptogenesis, while at a dosage of 200 mg/kg on 6th day LEV significantly suppressed paroxysmal activity in the studied structures of rats with cobalt epilepsy. The strongest anti-paroxysmal effect was detected in hippocampus and was expressed as the normalization of bioelectrical activity and the appearance of a regular theta rhythm. Thus, LEV effects are mostly directed to the hippocampal area of epileptiform activity and, to a lesser extent, to the cortical area.

The effect of short-term administration of (-)-deprenyl and isatin on the expressions of some genes in the mouse brain cortex.

BACKGROUND: Isatin (indoledione 2,3) is an endogenous indole found in the mammalian brain, peripheral tissues, and body fluids. It exhibits many neurophysiological and neuropharmacological effects. It shares some common molecular targets with (-)-deprenyl, a neuroprotective pharmacological drug. Some isatin effects imply a possible influence of gene expression; however, no isatin-responsive genes have yet been identified. MATERIAL/METHODS: In this study the effects of a three-week administration of isatin (20 mg/kg) or (-)-deprenyl (1 mg/kg) on the expressions of several putative isatin/deprenyl-responsive genes in the mouse cortex were compared using real-time PCR. RESULTS: Both treatments caused similarly significant decreases in superoxide dismutase (SOD) mRNA. Treatment of mice with either drug decreased glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, although only in the deprenyl-treated mice was this significant (p<0.01). No significant changes were found in cortex mRNA content of monoamine oxidase A or monoamine oxidase B. CONCLUSIONS: The results suggest that isatin and (-)-deprenyl have some common target genes and this supports the idea that isatin may be an endogenous partial functional agonist of (-)-deprenyl. Since GAPDH mRNA expression is sensitive to the pharmacological treatments, these results also question the applicability of GAPDH as a reference gene in gene expression studies.