Probucol inhibits neural cell apoptosis via inhibition of mTOR signaling pathway after spinal cord injury

- Probucol increases the expression of Beclin-1 and LC3B after SCI.
- The mTOR signal pathway is inhibited by probucol after SCI.
- Probucol reduces the expression of Caspase-3 and Caspase-9 after SCI.
- Probucol promotes the functional recovery of motor nerve after SCI.

Autophagy plays an essential role in neurodevelopment, axonal guidance, neuropathic pain remission, and neuronal survival. Inhibiting the mammalian target of rapamycin (mTOR) signaling pathway can induce the occurrence of autophagy. In this study, we initially detected the effect of probucol on autophagy after spinal cord injury (SCI) by intraperitoneally injecting spinal cord-injured rats with probucol for 7 days. The levels of Beclin1 and LC3B were evidently enhanced at 7 days post-operation. However, the increase in the phosphorylated AMP-activated protein kinase (AMPK) protein and the decrease in ribosomal protein S6 kinase p70 subtype (p70S6K) phosphorylation level simultaneously occurred after SCI. Moreover, the expression levels of apoptosis-related proteins of Caspase-3, Caspase-9, and Bax were significantly reduced. Immunofluorescence results indicated that the expression of Caspase-3 protein was evidently decreased and that of Beclin-1 protein was increased by probucol. Nissl staining and Basso, Beattie, and Bresnahan scores showed that the quantity and function of motor neurons were visibly preserved by probucol after SCI. This study showed that probucol inhibited the mTOR signaling pathway to induce autophagy, reduce neural cell apoptosis and promote recovery of neurological function after SCI.

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