Comparative transcriptome of neurons after oxygen-glucose deprivation: Potential differences in neuroprotection versus reperfusion.

In the context of ischemic stroke, rescuing neurons can be theoretically achieved with either reperfusion or neuroprotection. Reperfusion works via the rapid restoration of oxygen and glucose delivery. Neuroprotection comprises molecular strategies that seek to block excitotoxicity, oxidative stress or various cell death pathways. Here, we propose the hypothesis that neurons rescued with reperfusion are different from neurons rescued with molecular neuroprotection. Neurons were subjected to oxygen-glucose deprivation (OGD) and then treated with "in vitro reperfusion" (i.e. energetic rescue via restoration of oxygen and glucose) or Z-VADfmk (to block apoptosis) or MK-801 (to block excitotoxicity). Levels of injury were titrated so that equivalent levels of neuronal salvage were achieved with reperfusion or neuroprotection. Gene arrays showed that OGD significantly altered the transcriptomic profiles of surviving neurons. Pathway analysis confirmed that a large spectrum of metabolic, inflammation, and signaling genes were perturbed. In spite of the fact that equal levels of neuronal salvage were achieved, energetic rescue renormalized the transcriptomic profiles in surviving neurons to a larger degree compared to neuroprotection with either Z-VADfmk or MK-801. These findings suggest that upstream reperfusion may bring salvaged neurons back "closer to normal" compared to downstream molecular neuroprotection.

Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune diseases with focus on systemic lupus erythematosus.

Autoimmune diseases often share common susceptibility genes. Most genetic variants associated with susceptibility to systemic lupus erythematosus are also associated with other autoimmune diseases. The X-linked variant rs2294020 is positioned in exon 7 of the CCDC22 gene. The encoded protein functions in the regulation of NF-κB, a master regulator in immune response. The aim of this study is to investigate whether the rs2294020 polymorphism may be a general susceptibility factor for autoimmunity. We evaluated case-control association between the occurrence of rs2294020 and different autoimmune diseases, including new data for systemic lupus erythematosus and previous genome-wide association studies (GWAS) (though most did not analyse the X chromosome) of psoriasis, celiac disease, Crohn's disease, ulcerative colitis, multiple sclerosis, vitiligo, type-1 diabetes, rheumatoid arthritis, and ankylosing spondylitis. Cases from patients affected by amyotrophic lateral sclerosis and type-2 diabetes were also included in the study. We detected nominal significant associations of rs2294020 with systemic lupus erythematosus (additive model test: p=0.01), vitiligo (p=0.016), psoriasis (p=0.038), and in only one of two studies of multiple sclerosis (p=0.03). Our results suggest that rs2294020 is associated with the risk of several autoimmune diseases in European populations, specifically with diseases that present themselves, among else, in the skin.