Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.
J Chem Neuroanat
; 114: 101960, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33915267
ABSTRACT
BACKGROUND:
Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons leading to brain dysfunction. Recurrent seizures can lead to cognitive and behavioral deficits, and irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve), an mTOR inhibitor, may modulate neuronal excitability and therefore exert protection against epilepsy. Therefore, this study aimed to investigate the neuroprotective effect of Everolimus on seizure-induced brain injury and its regulation of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Kainic acid (KA) 15 mg/kg was used to induce seizures and Everolimus (1, 2, 5 mg/kg) was administered as a pretreatment. Hippocampal tissue was extracted 24 h post-seizure.RESULTS:
The protein and mRNA expression levels of PI3Kãp-AKtãp-mTORãNF-kB and IL-6 as well as neuronal apoptosis and microglia activation, significantly increased after KA-induced seizures, however, these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency.CONCLUSIONS:
Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Convulsões
/
Lesões Encefálicas
/
Transdução de Sinais
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Fármacos Neuroprotetores
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Everolimo
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article