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Grygoriy Tsenov

 

Grygoriy Tsenov

National Institute of Mental Health, Czech Republic

Abstract Title: The Neuroactive Steroid Pregnanolone Glutamate: antiepileptic, neuroprotective, and anti-inflammatory effect in perinatal focal cerebral ischemia model.

Biography: Grygoriy Tsenov has completed his PhD in Neuroscience from Charles University in Prague working on brain excitability changes in the perinatal status epilepticus model. Later, he focused on the role of endothelin receptors in the perinatal ischemic stroke model and treatment of perinatal ischemia outcome. He is the Leader of the Experimental Neurobiology group of the Preclinical Research Program at the National Institute of Mental Health (Czech Republic). He has published over 20 papers in renowned journals and supervises student diploma and dissertation theses at the Faculty of Science, Charles University.

Research Interest: The present study aims to explain the mechanism of the therapeutic effect of synthetic 3α5β pregnanolone glutamate (3α5β-PG) in a model of perinatal focal cerebral ischemia (FCI) using electrophysiological, immunohistochemical, and bioanalytical correlates. The effect of 3α5β-PG on the course of FCI itself and on the changes induced by FCI was studied in 12-day-old rats. FCI was induced by endothelin-1 infusion (ET-1; 40 pmol/1μl) into the right dorsal hippocampus. Electrodes were implanted contralaterally in the dorsal hippocampus and over the left sensorimotor cortex. The 3α5β-PG (1 mg/kg, i.p.) was administrated 5 minutes after the end of ET-1 infusion. Animals were EEG-monitored for 2h and parameters of electrographic seizures and power spectral density (PSD) changes were evaluated. Animals were transcardially perfused 24 hours later, brains were sectioned, and stained for markers of neurodegeneration and inflammation. Another group of animals without electrodes was sacrificed 1h after 3α5β-PG treatment, right hippocampi were harvested, and the steroidomic profile was analyzed by GC-MS/MS. Significant increases in pregnanolone (~40-fold), 17-hydroxypregnanolone (~9-fold), and allopregnanolone (~1.5-fold) were found in the hippocampi of animals injected with 3α5β-PG after ischemia. This confirms our previous findings that 3α5β-PG is a prodrug for 17-hydroxypregnanolone. Pregnanolone-glutamate treatment attenuated ischemia-induced seizures (~90%) significantly decreased PSD in all EEG bands and distinctly reduced inflammation and neurodegeneration after 24 hours compared to non-treated ischemic animals. These results demonstrate that 3α5β-PG can ameliorate the effects of ischemia in the immature brain. This study was supported by the GACR project 23-05746S and MHCZ–DRO (NUDZ, 00023752).