Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1

- Edaravone (EDV) pretreatment reversed the LPS-induced neurobehavioral anomalies.
- EDV pretreatment prevented LPS-induced oxido-nitrosative stress.
- EDV pretreatment ameliorated anomalous expression of PARP-1 and neuroinflammation.
- EDV pretreatment reversed LPS-induced serum high corticosterone and low BDNF levels.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1. Male Swiss albino mice were treated with edaravone (3 & 10 mg/kg i.p.) once daily for 14 days. On the 14th day 30 min after edaravone treatment mice were challenged with LPS (1 mg/kg i.p.). After 3 h and 24 h of LPS administration we've tested mice for anxiety and depressive-like behaviors respectively. Western blotting analysis of PARP-1 in hippocampus was carried out after 12 h of LPS administration. Moreover, after 24 h of LPS administration serum corticosterone, hippocampal BDNF, oxido-nitrosative stress and pro-inflammatory cytokines were estimated by ELISA. Results showed that pretreatment of edaravone (10 mg/kg) ameliorates LPS-induced anxiety and depressive-like behavior. Western blotting analysis showed that LPS-induced anomalous expression of PARP-1 significantly reverses by the pretreatment of edaravone (10 mg/kg).Biochemical analyses revealed that LPS significantly diminishes BDNF, increases pro-inflammatory cytokines and oxido-nitrosative stress in the hippocampus. However, pretreatment with edaravone (10 mg/kg) prominently reversed all these biochemical alterations. Our study emphasized that edaravone pretreatment prevents LPS-induced anxiety and depressive-like behavior, mainly by impeding the inflammation, oxido-nitrosative stress and PARP-1 overexpression.