Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats

Abstract

Abstract Purpose Diffuse axonal injury (DAI) is a critical pathological facet of traumatic brain injury (TBI). Oxidative stress plays a significant role in progress of DAI. Annexin A1 has been demonstrated benefit for recovery of neurofunctional outcomes after TBI. However, whether annexin A1 exhibits neuronal protective function through modulating oxidative stress in DAI remains unknown. Methods Expression of annexin A1 was evaluated via real time PCR and western blot analysis in rat brainstem after DAI. Neurological effect of annexin A1 following DAI through quantification of modified neurologic severity score (mNSS) was compared between wild-type and annexin A1-knockout rats. Brain edema and neuronal apoptosis, as well as expression of oxidative factors and inflammatory cytokines was analysed between wild-type and annexin A1 deficiency rats after DAI. Furthermore, mNSS, oxidative and inflammatory cytokines were assayed after timely administration of recombinant annexin A1 for DAI rats. Results In brainstem of DAI, the expression of annexin A1 remarkably increased. Ablation of annexin A1 increased mNSS score and brain water content of rats after DAI. Neuron apoptosis in brainstem after DAI was exaggerated by annexin A1 deficiency. In addition, annexin A1 deficiency significantly upregulated level of oxidative and inflammatory factors in brainstem of DAI rats. Moreover, mNSS decreased by annexin A1 treatment in rats following DAI. Expression of oxidative and inflammatory molecules in rat brainstem subjected to DAI inhibited by annexin A1 administration. Conclusions These results demonstrated that annexin A1 exhibits neuronal protective function in the progression of DAI mainly dependent on suppressing oxidative stress and inflammation.