Splenectomy following MCAO inhibits the TLR4–NF-κB signaling pathway and protects the brain from neurodegeneration in rats

Abstract

Background and purposeThe Toll-like receptor 4(TLR4)/nuclear factor kappa B NF-κB inflammatory pathway contributes to secondary inflammation in many diseases including stroke. Moreover, the neuroprotective effect of splenectomy in stroke is supported by a vast body of experimental evidence. Nevertheless, the underlying mechanism(s) by which splenectomy enhance neuroprotection in stroke is still poorly understood. Our study aimed to investigate whether post-ischemic splenectomy modulate the TLR4/NF-κB inflammatory pathway in stroke. MethodsImmunohistochemistry was used to evaluate the levels of TLR4 and NF-κB expression in brain areas (parietal lobe, hippocampus and striatum) of rats that underwent: MCAO-splenectomy surgery (MS ); MCAO surgery without splenectomy (MCAO control or MC); Sham MCAO and splenectomy surgery (sham control group or SC group respectively. Apoptosis in these areas was assessed by TUNEL detection technique. ResultsThe levels of TLR4 and NF-κB expression were significantly reduced in splenectomized rats relative to the MS group (P<0.01). Additionally, the number of apoptotic cells in the ischemic hemisphere were significantly higher in both MCAO groups compared to the Sham group (P<0.05), between day 1 and day 7. An exception was observed in the striatum where the difference in apoptotic rate between the MS and sham group was not statistically significant at the same time points. Moreover, the variation apoptotic rate in different cerebral zone correlated to variation in TLR4 and NF-κB expression. ConclusionIn summary, our study provides further evidence of neuroprotective effect of splenectomy in ischemic stroke. Our results suggest that such an effect might be due to the inhibition of theTLR4/NF-κB inflammatory pathway.