Edaravone Reduces Apoptosis Of Neural Cells In Rats With Acute Spinal Cord Injury Through The JAK2/STAT3 Signaling Pathway

Objective: Acute spinal cord injury(ASCI),being a disease with acute onset,high disability rate and large refractoriness,brings heavy burdens on both patients and their families.Therefor,the findings of effective treatment are the focus of current research.Edaravone(EDA)has been used as a neuroprotective agent in the clinical treatment for ASCI.The aim of this study was to identify whether the JAK2/STAT3 signaling pathway is involved in the protective effects of EDA on neural cells of rats with ASCI.Methods: 120 adult male SD rats were randomly divided into four groups: sham group,ASCI group,ASCI + EDA group(treated with 3mg/kg EDA),and ASCI + AG490 group(treated with 15mg/kg tyrosine kinase inhibitor AG490)(each=30).A modified Allen method was used to establish ASCI model a rat.BBB scores were used to evaluate hindlimb motor function at 1,3,7,14,21,and 28 d after surgery.HE staining was used to observe the spinal cord morphology of tissue in rats of each group at 28 d after surgery.TUNEL method was used to detect the apoptosis level of neural cells in rats of each group at 6,12,24,and 72 h after surgery.Also,in rats of each group at 6,12,24,and 72 h after surgery,the expression levels of p-JAK2 and p-STAT3,as well as Caspase-3 in tissues were determined by western-blot and immunostaining method,respectively.Results:1.In rats with ASCI,the hindlimb motor capacity was abnormal;the spinal cord morphology in tissues was changed;the BBB score was significantly decreased(P<0.05).EDA or AG490 treatment significantly increased the BBB score of rats with ASCI(P<0.05).However,there was no statistical difference between the two groups(P>0.05).2.In rats with ASCI,the apoptosis of neural cells in tissues was significantly increased at 6h(P<0.05),reached a peak at 72 h.EDA or AG490 treatment significantly decreased the apoptosis of neural cells in tissues of rats with ASCI(P<0.05).While there was no statistical difference between the two groups(P>0.05).3.In tissues of rats with ASCI,the expression level of both p-JAK2 and p-STAT3 was significantly increased at 6h(P<0.05),reached a peak at 12 h.The change in the expression level of p-JAK2 and p-STAT3 was significantly inhibited by EDA or AG490 treatment(P<0.05).However,there was no statistical difference between the two groups(P>0.05).4.In tissues of rats with ASCI,the expression level of Caspase-3 was significantly increased at 6h(P<0.05),reached a peak at 72 h.The change in the expression level of Caspase-3 was significantly inhibited by EDA or AG490 treatment(P<0.05).However,there was no statistical difference between the two groups(P>0.05).Conclusions:1.EDA promotes the recovery of motor function of rats with ASCI,which has a similar protective effect on neural cells with AG490.2.In tissues of rats with ASCI,EDA reduces the expression levels of p-JAK2,p-STAT3 and Caspase-3,decreases the apoptosis of neural cells,demonstrating that EDA has a neuroprotective effect.The potential mechanism may relevant to the inhibition of JAK2/ STAT3 signaling pathway.