L-carnosine inhibits neuronal cell apoptosis through signal transducer and activator of transcription 3 signaling pathway after acute focal cerebral ischemia

Abstract

Considerable studies have showed that L-carnosine provides anti-oxidative and anti-apoptotic roles in the animal models of global or focal cerebral ischemia. However, the anti-apoptotic mechanisms of L-carnosine in the focal cerebral ischemia model have yet to be elucidated. To investigate the molecular mechanisms, rat models of permanent middle cerebral artery occlusion (pMCAO) and sham operation were first established and then pMCAO and sham-operated rats were treated with L-carnosine or vehicle alone. After this treatment, neurological deficits were evaluated at 12, 24 and 72h after operation and the infarct volume was measured at 72h after treatment. In addition, we also detected the mRNA expression of signal transducer and activator of transcription 3 (STAT3) and Pim-1 and the protein expression of phosphorylated STAT3, Pim-1, bcl-2 and cleaved caspase-3 at 12, 24 and 72h post-pMCAO. Our results showed that the L-carnosine-treated rats had milder neurological deficits and smaller infarct volume and showed up-regulated expression in mRNA levels of STAT3 and Pim-1 than vehicle-treated rats at 72h after treatment. Meanwhile, compared with vehicle-treated rats, the L-carnosine-treated rats exhibited higher protein expressions of pSTAT3, Pim-1 and bcl-2 but lower expression of cleaved caspase-3 protein at 72h following operation. These results indicate that L-carnosine plays an important role in inhibiting neuronal cell apoptosis through STAT3 signaling pathway after acute cerebral ischemia.