Lipopolysaccharide preconditioning attenuates neuroapoptosis and improves functional recovery through activation of Nrf2 in traumatic spinal cord injury rats

Abstract

The previous studies suggested that low-dose lipopolysaccharide (LPS) provides neuroprotection against subsequent challenge with ischemic/reperfusion injury in the brain. But there were few reports about the neuroprotective effects of low-dose LPS against spinal cord injury (SCI). In this study, we evaluated the effect of low-dose LPS preconditioning on neuroapoptosis status after traumatic SCI (TSCI), using a standardized contusion model (NYU, New York University, impactor). SCI-induced rats were randomly divided into three groups: sham operation, control (receiving only normal saline) and LPS preconditioning (0.2 mg/kg, ip; 72 hours before injury). Neurologic function was assessed by the Basso, Beattie and Bresnahan (BBB) score at 6, 12, 24, 48 and 72 hours after TSCI. Rats were sacrificed at 72 hours postinjury. Histological changes were studied using Nissl staining. Apoptotic neural cells were assessed using the TdT-mediated dUTP Nick End Labeling (TUNEL) assay. Nuclear factor erythroid 2-related factor 2 (Nrf2) and caspase-3 were detected with immunohistochemistry and Western blot. LPS preconditioning reduced neuron apoptosis, improved neurologic outcome and actived Nrf2 expression. Moreover, Histological changes and the number of apoptotic cells were correlated with Nrf2 expression after the rats suffered the SCI. Our results suggest that LPS preconditioning exerted a neuroprotective effect against TSCI in rats, and activation of Nrf2 was believed to be one of the contributing mechanisms.