Myoinositol Attenuates the Cell Loss and Biochemical Changes Induced by Kainic Acid Status Epilepticus

Abstract

Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes. The increase in the amount of voltage-dependent anionic channel-1 (VDAC-1), cofilin, and caspase-3 activity was observed in the hippocampus of KA treated rats. Administration of MI 4 hours later after KA treatment abolishes these changes, whereas diazepam treatment by the same time schedule has no significant influence. The number of neuronal cells in CA1 and CA3 subfields of hippocampus is decreased after KA induced SE and MI posttreatment significantly attenuates this reduction. No significant changes are observed in the neocortex. Obtained results indicate that MI posttreatment after KA induced SE could successfully target the biochemical processes involved in apoptosis, reduces cell loss, and can be successfully used in the future for translational research.

Long-Term Effects of Myoinositol on Behavioural Seizures and Biochemical Changes Evoked by Kainic Acid Induced Epileptogenesis

“…Equal volume aliquots, containing 30 μ g protein, were applied to the sodium dodecyl sulphate (SDS) gels and electrophoresis and Western blotting were carried out as described previously [ 12 ]. After the protein had been transferred onto nitrocellulose membranes, the membranes were stained with Ponceau S solution and analyzed with Image J software ( https://imagej.net/ImageJ ) to confirm uniform gel loading and transfer.…”

“…After the protein had been transferred onto nitrocellulose membranes, the membranes were stained with Ponceau S solution and analyzed with Image J software ( https://imagej.net/ImageJ ) to confirm uniform gel loading and transfer. Standard immunochemical procedures were carried out using primary antibodies against HMGB1 (Abcam, ab18256) and peroxidase-labelled secondary antibodies and Super-Signal West Pico Chemiluminescent substrate (Pierce) [ 12 ]. The optical densities of bands, corresponding to the HMGB1 were measured using Lab Works 4.0 (UVP).…”

“…Optical density was proportional to the amounts of HMGB1 in either brain homogenates or plasma (see Figure 7 ). For the data analysis optical density of each sample band was divided by optical density of the band for 30 μ g of protein standard [ 12 ] to give “relative amount of protein”.…”

“…Namely, KA-induced epileptogenesis was characterized by a strong decrease (>60%) in the levels of AMPA-glutamate receptor GLUR1 subunit, calcium-calmodulin dependent protein kinase II (CaMKII), and gamma-2 subunit of GABA-receptor in the hippocampus and this decrease was nearly completely reversed by MI daily treatment [ 10 , 11 ]. We have suggested that the effects of MI at least partially should be mediated by its osmolyte properties [ 10 – 12 ].…”

Myo-Inositol Limits Kainic Acid-Induced Epileptogenesis in Rats

“…In our previous study, we showed neuronal cell loss observed 24 h after KA induced SE in the hippocampus, and MI treatment had a protective effect on cell death [19]. Here we have analyzed whether KA and MI treatment effects in the hippocampus was still observed 8 weeks after SE.…”