Unfavorable effect of levetiracetam on cultured hippocampal neurons after hyperthermic injury
Autor: | Małgorzata Rusak, Krzysztof Sendrowski, Elżbieta Poskrobko, Wojciech Sobaniec, Piotr Sobaniec |
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Rok vydání: | 2017 |
Předmět: |
Hyperthermia
Programmed cell death Levetiracetam Fever Cell Survival Population Apoptosis Hippocampal formation Pharmacology Hippocampus Neuroprotection Flow cytometry Rats Sprague-Dawley Necrosis 03 medical and health sciences 0302 clinical medicine Annexin medicine Animals education Cells Cultured Neurons education.field_of_study Cell Death Dose-Response Relationship Drug L-Lactate Dehydrogenase medicine.diagnostic_test Chemistry General Medicine medicine.disease Piracetam Rats Neuroprotective Agents 030220 oncology & carcinogenesis Anticonvulsants 030217 neurology & neurosurgery |
Zdroj: | Pharmacological Reports. 69:462-468 |
ISSN: | 1734-1140 |
Popis: | Background The aim of this study was to examine the viability of neurons and the putative neuroprotective effects of second-generation antiepileptic drug, levetiracetam (LEV), on cultured hippocampal neurons injured by hyperthermia. Methods Primary cultures of rat's hippocampal neurons at 7 day in vitro (DIV) were incubated in the presence or absence of LEV in varied concentrations under hyperthermic conditions. Cultures were heated in a temperature of 40 °C for 24 h or in a temperature of 41 °C for 6 h. Flow cytometry with Annexin V/PI staining as well as fluorescent microscopy assay were used for counting and establishing neurons as viable, necrotic or apoptotic. Additionally, the release of lactate dehydrogenase (LDH) to the culture medium, as a marker of cell death, was evaluated. Assessment was performed after 9DIV and 10 DIV. Results Incubation of hippocampal cultures in hyperthermic conditions resulted in statistically significant increase in the number of injured neurons when compared with non-heated control cultures. Intensity of neuronal destruction was dependent on temperature-value. When incubation temperature 40 °C was used, over 80% of the population of neurons remained viable after 10 DIV. Under higher temperature 41 °C, only less than 60% of neurons were viable after 10 DIV. Both apoptotic and necrotic pathways of neuronal death induced by hyperthermia were confirmed by Annexin V/PI staining. Conclusions LEV showed no neuroprotective effects in the current model of hyperthermia in vitro . Moreover, drug, especially when used in higher concentrations, exerted unfavorable intensification of aponecrosis of cultured hippocampal neurons. |
Databáze: | OpenAIRE |
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