Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Version 1 : Received: 24 September 2023 / Approved: 25 September 2023 / Online: 26 September 2023 (05:16:16 CEST)

A peer-reviewed article of this Preprint also exists.

Zubareva, O.E.; Sinyak, D.S.; Kalita, A.D.; Griflyuk, A.V.; Diespirov, G.P.; Postnikova, T.Y.; Zaitsev, A.V. Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats. Int. J. Mol. Sci. 2023, 24, 15400. Zubareva, O.E.; Sinyak, D.S.; Kalita, A.D.; Griflyuk, A.V.; Diespirov, G.P.; Postnikova, T.Y.; Zaitsev, A.V. Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats. Int. J. Mol. Sci. 2023, 24, 15400.

Abstract

Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no preventive therapy for epilepsy is currently available. The purpose of this study was to evaluate the effects of anakinra, lamotrigine, and their combination on epileptogenesis using the rat lithium-pilocarpine model of temporal lobe epilepsy. The study showed that the treated and untreated animals showed no significant difference in the number and duration of seizures. However, the severity of seizures was significantly reduced after treatment. Anakinra and lamotrigine, alone or in combination, significantly reduced neuronal loss in the CA1 hippocampus compared to the control group. However, the drugs administered alone were found to be more effective for CA3 than their combination. The treatment alleviated the impairments in activity level, exploratory behavior and anxiety, but had a relatively weak effect on TLE-induced impairments in social behavior and memory. The efficacy of the combination treatment did not differ from that of anakinra and lamotrigine monotherapy. These findings suggest that anakinra and lamotrigine, alone or in combination, may have clinical utility in preventing epileptogenesis.

Keywords

temporal lobe epilepsy; anakinra; lithium–pilocarpine model; behavior; epileptogenesis; hippocampus; spontaneous recurrent seizures; neuronal loss

Subject

Biology and Life Sciences, Neuroscience and Neurology

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