IRE1α/TRAF2/NF-κB pathway promotes apoptosis via regulating inflammatory cytokines and aggravates brain injury after SAH.

Abstract

Objectives: To investigate the effect of IRE1α/TRAF2/NF-κB pathway on early brain injury.

Methods: An endovascular puncture model of subarachnoid hemorrhage (SAH) was developed and SAH grading was performed. The following groups of experimental animals were randomly assigned: Blank group, Sham group, SAH+ DMSO group, SAH+STF-083010(IRE1α inhibitor) group, and SAH+BAY11-7082(NF-κB inhibitor) group. Neurological deficits were assessed in the animal models using a modified Garcia score. The expression of IRE1α, GRP78, TRAF2, NF-κB, and caspase3 was measured using western blot analysis. The concentrations of TNF-α, IL-1β and IL-6 were evaluated with ELISA kits. An analysis of neuronal apoptosis was performed using TUNEL staining.

Results: The neurological deficits, expression of IRE1α/TRAF2/NF-κB axis and its related proteins, inflammatory cytokines and apoptosis were increased after SAH, whereas their expressions were suppressed since the inhibition of the IRE1α/TRAF2/NF-κB signal pathway. Moreover, correlation analysis showed that TNF-α, IL-1β and IL-6 were positively correlated with apoptosis.

Conclusions: The IRE1α/TRAF2/NF-κB signal pathway was activated and promoted apoptosis by promoting the expression of inflammatory cytokines after SAH.