Objective: To explore the neuroprotective effects of preconditioning with low-dose lipopolysaccharide (LPS) in rats after spinal cord injury and its possible mechanism.
Methods: Forty-eight female SD rats were randomly divided into four groups as follows: empty virus (EV), LPS combined with empty virus (LPS-EV), nuclear factor erythroid 2-related factor 2 (Nrf2) interference virus (NIV), and LPS combined with Nrf2 interference virus (LPS-NIV) (n=12 per group). The model of traumatic spinal cord injury (TSCI) was established by the modified Allen's method. Hind limb motor function of the rats was assessed by the Basso, Beattie and Bresnahan (BBB) score 3 days after the operation. The injured spinal cord tissues were harvested after the operation. The pathological changes of spinal cord were observed by HE staining. The Nissl body and neuron survival index were assessed by Nissl staining. The expressions of Nrf2, NF-κB and associated pro-inflammatory cytokines (IL-1β, TNF-α) were detected by immunohistochemical staining and Western blotting.
Results: NIV group showed descended Nrf2 protein expression and ascended NF-κB, IL-1β, TNF-α protein levels compared with EV group, and no significant difference from LPS-NIV group. The Nrf2 protein expression of LPS-EV group increased significantly compared with EV group and LPS-NIV group, and NF-κB, TNF-α and IL-1β protein expression decreased significantly at the same time. Compared with those of EV group and LPS-NIV group, the neuron survival index of LPS-EV group was improved. The morphological change of LPS-EV group was also obviously alleviated. The BBB score had no statistical significance among these groups.
Conclusion: Low-dose LPS preconditioning had neuroprotective effects on spinal cord injury. This protective effect was mediated by activating the Nrf2 to down-regulate expressions of NF-κB and pro-inflammatory cytokines and alleviate inflammatory response.