Abstract
Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS). A complex pathophysiological process referred to as epileptogenesis transforms a normal brain into an epileptic one. Prevention of epileptogenesis is a subject of intensive research. Currently, there are no clinically approved drugs that can act as preventive medication. Our previous studies have revealed highly promising antiepileptogenic properties of a compound–myo-inositol (MI) and the present research broadens previous results and demonstrates the long-term disease-modifying effect of this drug, as well as the amelioration of cognitive comorbidities. For the first time, we show that long-term treatment with MI: (i) decreases the frequency and duration of electrographic SRS in the hippocampus; (ii) has an ameliorating effect on spatial learning and memory deficit associated with epileptogenesis, and (iii) attenuates cell loss in the hippocampus. MI treatment also alters the expression of the glial fibrillary acidic protein, LRRC8A subunit of volume-regulated anion channels, and protein tyrosine phosphatase receptor type R, all expected to counteract the epileptogenesis. All these effects are still present even 4 weeks after MI treatment ceased. This suggests that MI may exert multiple actions on various epileptogenesis-associated changes in the brain and, therefore, could be considered as a candidate target for prevention of epileptogenesis.
Highlights
Introduction iationsEpileptogenesis is a dynamic and multifactorial process of molecular, cellular, and network changes that cause certain structural and functional reorganization of the brain, in many cases induced by the precipitating events or insults
In the follow-up studies, we demonstrated that MI treatment attenuated molecular changes related to the kainic acid (KA)-induced epileptogenesis [14,15]
We asked whether MI treatment could prevent this impairment, and have shown that KA + MI group were performing significantly better in Morris water maze (MWM)
Summary
Epileptogenesis is a dynamic and multifactorial process of molecular, cellular, and network changes that cause certain structural and functional reorganization of the brain, in many cases induced by the precipitating events or insults. This process leads to the development of epilepsy—a disease that is characterized by spontaneous recurrent seizures (SRS) [1]. The International League against epilepsy defines epilepsy by the existence of two unprovoked seizures >24 h apart [2]. 1% of the world population suffers from epilepsy. Available antiseizure medications (ASMs) do not prevent or cure epilepsy and offer only symptomatic relief by suppressing SRS.
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