Inositols and epilepsy

Solomonia, Revaz and Lepsveridze, Eka and Kiguradze, Tamar and Nozadze, Maia (2013) Inositols and epilepsy. In: Inositol Synthesis, Functions and Clinical implications. NOVA BIOMEDICAL, New York, pp. 105-127.

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Epilepsy is a heterogeneous group of disorders. It is the most common neurological disorder after stroke. Despite the progress in the treatment of epilepsy, about one third of the patients with epilepsy are resistant to current pharmacotherapies. The current treatment of epilepsy focuses exclusively on preventing or suppressing seizures, which are symptoms of the underlying disease. The most important challenge is to prevent epileptogenesis, the process by which brain becomes epileptic. Drugs that prevent the development of epilepsy are not yet available. The central nervous system is characterized with relatively high concentrations of myo-inositol (MI) as well as the means to synthesize it. MI serves not only as a precursor molecule for inositol lipid synthesis, but also as a physiologically important osmolyte. Alteration in MI deposition may play a role in a number of neuropathological conditions, either as a physiologically important osmolyte or as a precursor molecule for phosphoinositide synthesis. Our data indicates for the role of MI in the regulation of seizures and the process of epileptogenesis. We have revealed that water extract of medicinal plant Aquilegia vulgaris (plant widely used in Oriental folk medicine as antiepileptic and soporific medicaments) contains compounds altering binding of ligands to the benzodiazepine and gamma-aminobuturic acid (GABA) binding sites of the GABA-A receptors. We have identified two such compounds of this extract: (1) (MI) and (2) sleep-inducing lipid oleamide. Further we have shown that MI and scyllo-inositol pretreatment significantly decreases the severity of seizures induced either by pentylentetrazolium or kainic acid (KA). As these effects were achieved by physiological concentrations of the administered inositoles, we have hypothetised that MI and SCI could represent endogenous anti-convulsants. MI also could interfere with the process of epileptogenesis. We have first induced statues epilepticus by KA and then applied MI daily treatment. We have shown that MI treatment during 28 days significantly attenuates biochemical changes associated with the process of epileptogenesis in hippocampus, and restores the level of some drastically reduces proteins to a normal level [4]. To these proteins belongs GLUR1 subunit of glutamate receptors, calcium/calmodulin dependent protein kinase II (CaMKII), 2 subunit of GABA-A receptors. The obtained results indicate that MI treatment at least could modify the epileptogenesis process induced by a brain insult. Further stuides of MI and SCI action could lead to more successful translational research and development of inositols as future anti-epileptic compounds.

Item Type: Book Section
Subjects: Q Science > QP Physiology
Divisions: Faculties/Schools > Faculty of Arts and Sciences
Depositing User: Dr. Eka Lepsveridze
Date Deposited: 07 Apr 2015 09:41
Last Modified: 30 Jun 2016 12:22

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