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Myo-Inositol Limits Kainic Acid-Induced Epileptogenesis in Rats
Authors:Manana Kandashvili  Georgi Gamkrelidze  Lia Tsverava  Tamar Lordkipanidze  Eka Lepsveridze  Vincenzo Lagani  Maia Burjanadze  Manana Dashniani  Merab Kokaia  Revaz Solomonia
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.
Keywords:myo-inositol  kainic acid  epilepsy  epileptogenesis  electrographic seizures  learning and memory  glial fibrillary acidic protein  volume regulated anionic channel  protein tyrosine phosphatase receptor type R
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