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Long-term effects of myoinositol on behavioural seizures and biochemical changes evoked by kainic acid induced epileptogenesis

Tsverava, Lia; Kandashvili, Manana; Margvelani, Giorgi; Lortkipanidze, Tamar; Gamkrelidze, Georgi; Lepsveridze, Eka; Kokaia, Merab LU and Solomonia, Revaz (2019) In BioMed Research International 2019.
Abstract

Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain-a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or formodification of disease progression.We have previously shown that (i)myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration ofMI for 4 weeks prevents certain... (More)

Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain-a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or formodification of disease progression.We have previously shown that (i)myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration ofMI for 4 weeks prevents certain biochemical changes triggered by SE. However it was not established whether such MI treatment also exerts long-term effects on the frequency of SRS. In the present study we have shown that, in KA-induced post-SE epilepsymodel in rats,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. Moreover, MI has significant effects on molecular changes in the hippocampus, includingmi-RNA expression spectrum, as well asmRNA levels of sodium-MI transporter and LRRC8A subunit of the volume regulated anionic channel. Taken together, these data suggest that molecular changes induced by MI treatment may counteract epileptogenesis.Thus, here we provide data indicating antiepileptogenic properties of MI, which further supports the idea of developing new antiepileptogenic and disease modifying drug that targetsMI system.

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organization
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Contribution to journal
publication status
published
subject
in
BioMed Research International
volume
2019
publisher
Hindawi Publishing Corporation
external identifiers
  • scopus:85062880338
ISSN
2314-6133
DOI
10.1155/2019/4518160
language
English
LU publication?
yes
id
3251fbea-4104-4274-8328-7968eca98cba
date added to LUP
2019-03-21 14:39:04
date last changed
2019-04-23 04:47:18
@article{3251fbea-4104-4274-8328-7968eca98cba,
  abstract     = {<p>Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain-a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or formodification of disease progression.We have previously shown that (i)myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration ofMI for 4 weeks prevents certain biochemical changes triggered by SE. However it was not established whether such MI treatment also exerts long-term effects on the frequency of SRS. In the present study we have shown that, in KA-induced post-SE epilepsymodel in rats,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. Moreover, MI has significant effects on molecular changes in the hippocampus, includingmi-RNA expression spectrum, as well asmRNA levels of sodium-MI transporter and LRRC8A subunit of the volume regulated anionic channel. Taken together, these data suggest that molecular changes induced by MI treatment may counteract epileptogenesis.Thus, here we provide data indicating antiepileptogenic properties of MI, which further supports the idea of developing new antiepileptogenic and disease modifying drug that targetsMI system.</p>},
  articleno    = {4518160},
  author       = {Tsverava, Lia and Kandashvili, Manana and Margvelani, Giorgi and Lortkipanidze, Tamar and Gamkrelidze, Georgi and Lepsveridze, Eka and Kokaia, Merab and Solomonia, Revaz},
  issn         = {2314-6133},
  language     = {eng},
  publisher    = {Hindawi Publishing Corporation},
  series       = {BioMed Research International},
  title        = {Long-term effects of myoinositol on behavioural seizures and biochemical changes evoked by kainic acid induced epileptogenesis},
  url          = {http://dx.doi.org/10.1155/2019/4518160},
  volume       = {2019},
  year         = {2019},
}