Salidroside alleviates ischemic brain injury in mice with ischemic stroke through regulating BDNK mediated PI3K/Akt pathway.

There is evidence suggesting that inhibition of apoptosis plays a critical role in preventing neurons from damage and even death, after brain ischemia/reperfusion, which shows therapeutic potential for clinical treatment of brain injury. In this study, We preformed MCAO model in C57BL/6J wild-type (BDNK+/+) and BDNK knockout (BDNF-/-) mice respectively, and investigated the neuroprotective effect of Salidroside (Sal) and its underlying mechanisms. The results showed that Sal reversed brain infarct size, reduced cerebral edema, decreased the neurological deficit score and diminished TUNEL positive cells significantly. However, BDNK deficiency inhibited the neuroprotective effect of Sal. In addition, Sal increased cell viability, ameliorated neuron cell injury by decreasing LDH activity, and inhibited cell apoptotic rate. Sal suppressed apoptotic signaling via DNA-binding-dependent and -independent mechanisms. Furthermore, the neuroprotective effect of Sal on BDNK was mediated by PI3K/Akt pathway, which was proved by the use of PI3K knockout (PI3K-/-) mice and siRNA-PI3K. In summary, these data strongly suggested that Sal could be used as an effective neuroprotective agent to protect against ischemic stroke after cerebral I/R injury through regulating BDNK-mediated PI3K/Akt apoptotic pathway in DNA-binding-dependent and -independent manners.