P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus

Background: the release of tumor necrosis factor-α (tnf-α) appears depend on the p2x7 receptor,a purinergic receptor. in the present study,we addressed the question of whether p2x7 receptor-mediated tnf-α regulation is involved in pathogenesis and outcome of status epilepticus (se).methods: se was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-,2',3'-o-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (bzatp),adenosine 5'-triphosphate-2',3'-dialdehyde (oxatp),a-438079,or a-740003 prior to se induction. thereafter,we performed fluoro-jade b staining and immunohistochemical studies for tnf-α and nf-κb subunit phosphorylations.results: following se,p2x7 receptor agonist (bzatp) infusion increased tnf-α immunoreactivity in dentate granule cells as compared with that in saline-infused animals. in addition,tnf-α immunoreactivity was readily apparent in the mossy fibers,while tnf-α immunoreactivity in ca1-3 pyramidal cells was unaltered. however,p2x7 receptor antagonist (oxatp-,a-438079,and a-740003) infusion reduced se-induced tnf-α expression in dentate granule cells. in the ca3 region,bzatp infusion attenuated se-induced neuronal damage,accompanied by enhancement of p65-ser276 and p65-ser311 nf-κb subunit phosphorylations. in contrast,oxatp-,a-438079,and a-740003 infusions increased se-induced neuronal death. soluble tnf p55 receptor (stnfp55r),and cotreatment with bzatp and stnfp55r infusion also increased se-induced neuronal damage in ca3 region. however,oxatp-,stnfp55r or bzatp+stnfp55r infusions could not exacerbate se-induced neuronal damages in the dentate gyrus and the ca1 region,as compared to bzatp infusion.conclusions: these findings suggest that tnf-α induction by p2x7 receptor activation may ameliorate se-induced ca3 neuronal damage via enhancing nf-κb p65-ser276 and p65-ser311 phosphorylations. © 2011 kim et al; licensee biomed central ltd.