PI3K/Akt and ERK1/2 pathways are responsible for sodium butyrateinduced inhibition of neuronal apoptosis in rats with cerebral infarction

The aim of this study was to elucidate the neuronal protection effect of sodium butyrate (NaB) on neuronal apoptosis in rats with cerebral infarction (CI), and the involvement of the phosphatidilinositol 3-kinase/protein kinase B (PI3K/Akt) and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways. MI model in rats was performed by middle cerebral artery occlusion (MCAO). Three hours after reperfusion, gastric administration of 5 or 10 mg/kg NaB was performed. Neurological deficit score, infarct size and brain edema were evaluated in rats after 24 h of reperfusion. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine contents of oxidative stress factors. Lactate dehydrogenase (LDH) activity, cell viability and apoptosis in extracted neurons were determined. Moreover, expression levels of Bcl-2, Bax, Akt and ERK1/2 were examined. NaB treatment markedly reduced infarct size and brain edema content in CI rats, and NaB treatment improved viability, decreased LDH activity and reversed contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in a dose-dependent manner. In addition, NaB treatment dose-dependently reduced apoptotic rate and Bax level, as well as enhanced Bcl-2 level. Protein levels of Akt and ERK1/2 were markedly upregulated in NaB-treated neurons. NaB treatment alleviates neuronal apoptosis via the PI3K/Akt and ERK1/2 pathways in CI rats, thus protecting the deterioration of CI.