Protective profile of oxcarbazepine against oxygen-glucose deprivation in organotypic hippocampal slice culture could involve PI3K cell signaling pathway.
OBJECTIVE
Brain ischemia results in cellular degeneration and loss of brain function. Oxcarbazepine (OXC), one of the newer antiepileptic drugs, has been demonstrating its efficacy on wide spectrum neurological disorders. In this paper, we investigated the neuroprotective profile of OXC in an in vitro model of ischemia, which consists in the exposure of organotypic hippocampal slice cultures to oxygen and glucose deprivation.


METHODS
OXC (30 microM) was added to the medium before and/or during and/or after the oxygen and glucose deprivation induction. Cell death was quantified by propidium iodide uptake measurement. Immunoblotting was used to detect the phosphorylation of Akt.


RESULTS
Our results showed a decrease in propidium iodide incorporation when OXC was added before oxygen and glucose deprivation, suggesting a neuroprotective effect. This effect was prevented when cultures were previously treated with LY294002, an inhibitor of phosphoinositide-3-kinase (PI3K) pathway. We also analysed the effect of OXC on Akt phosphorylation. Immunoblotting revealed that OXC did not induce any change in phosphorylation/activation of Akt.


CONCLUSIONS
Our results reinforce the neuroprotective effect of OXC and add some evidence that its mechanism may involve the PI3K pathway, suggesting that such effect could be upstream Akt. This indicates that with respect to OXC neuroprotective, Akt may not play a crucial role in determining cell survival.
Simão
Fabrício
F
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
Zamin
Lauren L
LL
Frozza
Rudimar
R
Nassif
Melissa
M
Horn
Ana Paula
AP
Salbego
Christianne G
CG
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D015153:Blotting, Western; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D019610:Cytoprotection / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009410:Nerve Degeneration / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D000078330:Oxcarbazepine; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D000927:Anticonvulsants; D002220:Carbamazepine; D002867:Chromones; D004791:Enzyme Inhibitors; D005947:Glucose; D009025:Morpholines; D000078330:Oxcarbazepine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one