Figure 8.

Potential action mechanisms of metformin against SCI. Following the primary insult, structural damage and a loss of homeostasis trigger the disturbance of energy metabolism, oxidative stress, mitochondrial disorder, endoplasmic reticulum stress, and increased mTORC1 expression. Metformin, the activator of AMPK and well-antioxidant, can modulate the AMPK and reverse electron flow in mitochondria to suppress the ROS generation and activation of NLRP3 inflammasome or NF-κB signaling, ameliorate endoplasmic reticulum stress to regulate the Bcl-2 and caspase-3, attenuate mTORC1 activation to induce the autophagosome formation, thereby exerting a satisfactory neuroprotective role in SCI rat.