TRANSLATIONAL AND CLINICAL MEDICINE - Georgian Medical Journal

Background. Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS) and affects 1% of human population. 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 and of great biomedical importance. Currently, there are no clinically approved drugs that can act as preventive medication.

Aims. Our previous studies have revealed highly promising antiepileptogenic properties of a compound–myo-inositol (MI) and the present research is aimed to broaden previous results and demonstrate  the long-term disease-modifying effect of this drug, as well as the amelioration of cognitive comorbidities.

Materials and Methods. Status epilepticus (SE) was induced by kainic acid (KA) injections. MI and saline treatment was continued for 4 weeks. Electrophysiological recordings in the hippocampus, morphological and biochemical analysis and Morris water maze experiments were conducted 8 week after the SE.

Results. MI treatment for 28 days reduces frequency and duration of behavioural SRS  not only during the treatment, but also after its termination for the following 4 weeks. 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), ttenuates cell loss in the CA1 and CA3 subfields of hippocampus and (iii) has an ameliorating effect on spatial learning and memory deficit associated KA induced with epileptogenesis

MI treatment alters micro-RNA expression spectrum and  decreases  the level of the glial fibrillary acidic protein. The expression of sodium-MI transporter,  LRRC8A subunit of volume-regulated anion channels, micro-RNA 6216 and its target - protein tyrosine phosphatase receptor type R, are altered in a such way  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.

Conclusion. Obtained data our could  open novel possibilities to develop  MI treatment as possible future approach  for preventive strategy to modify disease initiating process and its progress -epileptogenesis - and lay foundation for further translational development of the MI research.

References

1. Tsverava et al., BioMed Research International,  2019, Article ID 4518160.
2. Kandashvili et al., 2022, Int J Mol Sci., 23:1198