Aspirin Exerts Neuroprotective Effects By Activating Nrf2/HO-1 Signaling Pathway After Spinal Cord Injury

ObjectiveTo investigate the effects of aspirin on the apoptosis of neural cells and neurological function recovery after spinal cord injury.MethodsThe rats were randomly divided into three groups: aspirin group(aspirin,n= 22),DMSO group(Vehicle,n = 22)and sham group(Sham,n = 22,laminectomy only).The spinal cord injury was established by Allen's method.Aspirin(20 mg / kg)and DMSO as control were injected intraperitoneally immediately.At the same time point on the first day and the second day after spinal cord injury,the same dose of aspirin and control solvent were injected.The BBB score was used to observe the motor function of the hind limbs in different treatment groups at 1,3,7,14,21 and 28 days after injury.The expressions of Nrf2/HO-1 signaling pathway proteins(Nrf2,NQO1 and HO-1),apoptosis-related proteins(Bax,Bcl-2,caspase-3 and cleaved caspase-3)and inflammation-related proteins were detected by western blot on day 7.Immunofluorescence staining was used to detected the colocalization of NeuN and HO-1.At the same time,the expressions of GFAP was detected by Immunofluorescence.Nissl staining was used to detect the neurons of the spinal cord anterior horn.The changes of apoptotic in motor neurons of the tissue were observed by TUNEL staining.ResultsAt 7 days and subsequent point in time after spinal cord injury,aspirin significantly promoted the recovery of hind limb motor function(p <0.01).The expression of Nrf2,NQO1,and HO-1 proteins was increased in aspirin-treatedanimals after SCI compared with the vehicle group.In addition,aspirin simultaneously decreased the expression of inflammation-related proteins,such as TNF-? and IL-6 after SCI.Moreover,the ratio of apoptotic neurons in the anterior horn and the levels of the apoptosis-related proteins caspase-3,cleaved caspase-3,and Bax were decreased.Immunofluorescence staining was used to detect the colocalization of NeuN and HO-1,and the results showed that aspirin significantly increased expression of the HO-1 protein in neurons.In addition,western blots and immunofluorescence staining showed aspirin restrained astrocyte activation.ConclusionsIn conclusion,aspirin induces neuroprotective effects by inhibiting astrocyte activation,inflammation and neuronal apoptosis after SCI through the activation of the Nrf2/HO-1 signaling pathway.