Adiponectin Attenuates Oxygen–Glucose Deprivation-Induced Mitochondrial Oxidative Injury and Apoptosis in Hippocampal HT22 Cells via the JAK2/STAT3 Pathway

Ischemic stroke is among the leading causes of morbidity and mortality worldwide. Improving the tolerance of neurons to ischemia and reperfusion injury could be a feasible strategy against ischemia. Adiponectin (APN) is a major adipokine that regulates glucose and lipid metabolism and plays an important role in the protection of the cerebral nervous system. We aimed to investigate the effects of APN on oxygen and glucose deprivation (OGD)-induced neuronal injury in hippocampal neuronal HT22 cells. APN displayed neuroprotective effects against OGD, evidenced by increased cell viability and decreased lactate dehydrogenase release and apoptotic rate. Additionally, APN also maintained mitochondrial ultrastructure and transmembrane potential, attenuated reactive oxygen species and malondialdehyde, and increased superoxide dismutase and glutathione peroxidase activity. Moreover, APN promoted Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) phosphorylation, enhanced STAT3 nuclear translocation, increased the Bcl-2/Bax ratio, and decreased cleaved caspase-3. The aforementioned APN-induced effects were almost reversed by a JAK2 inhibitor, AG490. APN may attenuate OGD-induced hippocampal HT22 neuronal impairment by protecting cells against mitochondrial oxidative stress and apoptosis, mediated by JAK2/STAT3 signaling.