Epilepsy Research, volume 137, pages 84-94
Fatty acid amide hydrolase inhibitor URB597 may protect against kainic acid–induced damage to hippocampal neurons: Dependence on the degree of injury
Publication type: Journal Article
Publication date: 2017-11-01
Journal:
Epilepsy Research
Quartile SCImago
Q2
Quartile WOS
Q3
Impact factor: 2.2
ISSN: 09201211, 18726844
Neurology
Neurology (clinical)
Abstract
Status epilepticus (SE) provokes changes, which lead to neuronal alterations. Endocannabinoids (eCBs) can affect the neuronal survival during excitotoxicity and brain damage. Using a kainic acid (KA)-induced experimental SE model, we investigated whether cellular changes entail damage to endoplasmic reticulum (ER), mitochondria, and nuclei in hippocampal cells (CA1 field), and whether these alterations can be diminished by treatment with URB597, an inhibitor of eCB enzymatic degradation.SE was induced in Wistar rats by the microinjection of KA into the lateral ventricle. URB597 or a vehicle (10% DMSO) were injected in the same way into the brain of animals 24h after the KA infusion and then daily for the next nine days. The behavior of animals was controlled visually and recorded with a video system. The intensity of SE significantly varied in different animals. Convulsive (stages 3-5 according to the Racine scale) and nonconvulsive seizures (mainly stages 1, 2 and rarely 3, 4) were recognized.Two weeks after SE, a significant loss of hippocampal cells occurred in animals with KA injections. In survived cells, ultrastructural alterations in ER, mitochondria, and nuclei of hippocampal neurons were observed. The degree of cell injury depended on the severity of SE. Alterations evoked by moderate seizures were prevented or diminished by URB597, but strong seizures induced mostly irreversible damage.The beneficial impact of the FAAH inhibitor URB597 can give impetus to the development of novel neuroprotective strategies.
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- Statistics recalculated weekly.
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Mikheeva I. B. et al. Fatty acid amide hydrolase inhibitor URB597 may protect against kainic acid–induced damage to hippocampal neurons: Dependence on the degree of injury // Epilepsy Research. 2017. Vol. 137. pp. 84-94.
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Mikheeva I. B., Shubina L., Matveeva N., Pavlik L. L., Kitchigina V. Fatty acid amide hydrolase inhibitor URB597 may protect against kainic acid–induced damage to hippocampal neurons: Dependence on the degree of injury // Epilepsy Research. 2017. Vol. 137. pp. 84-94.
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TY - JOUR
DO - 10.1016/j.eplepsyres.2017.09.017
UR - https://doi.org/10.1016%2Fj.eplepsyres.2017.09.017
TI - Fatty acid amide hydrolase inhibitor URB597 may protect against kainic acid–induced damage to hippocampal neurons: Dependence on the degree of injury
T2 - Epilepsy Research
AU - Mikheeva, Irina B.
AU - Shubina, Liubov
AU - Pavlik, Luybov L
AU - Matveeva, Nataliya
AU - Kitchigina, V.F.
PY - 2017
DA - 2017/11/01 00:00:00
PB - Elsevier
SP - 84-94
VL - 137
SN - 0920-1211
SN - 1872-6844
ER -
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@article{2017_Mikheeva,
author = {Irina B. Mikheeva and Liubov Shubina and Luybov L Pavlik and Nataliya Matveeva and V.F. Kitchigina},
title = {Fatty acid amide hydrolase inhibitor URB597 may protect against kainic acid–induced damage to hippocampal neurons: Dependence on the degree of injury},
journal = {Epilepsy Research},
year = {2017},
volume = {137},
publisher = {Elsevier},
month = {nov},
url = {https://doi.org/10.1016%2Fj.eplepsyres.2017.09.017},
pages = {84--94},
doi = {10.1016/j.eplepsyres.2017.09.017}
}
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