Apolipoprotein E gene polymorphism and the risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies.

BACKGROUND: Studies investigating the association between the apolipoprotein E (APOE) gene polymorphism and the risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. METHODS: Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratio (OR) and 95% confidence interval (CI) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. RESULTS: This meta-analysis included 11 case-control studies, which included 1,238 ICH cases and 3,575 controls. The combined results based on all studies showed that ICH cases had a significantly higher frequency of APOE ϵ4 allele (OR= 1.42, 95% CI= 1.21,1.67, P<0.001). In the subgroup analysis by race, we also found that ICH cases had a significantly higher frequency of APOE ϵ4 allele in Asians (OR= 1.52, 95% CI= 1.20,1.93, P<0.001) and in Caucasians (OR= 1.34, 95% CI= 1.07,1.66, P=0.009). There was no significant relationship between APOE ϵ2 allele and the risk of ICH. CONCLUSION: Our meta-analysis suggested that APOE ϵ4 allele was associated with a higher risk of ICH.

Iduna contributes to the therapeutic effect of DHA in a cell and mouse model of traumatic brain injury via Wnt/MDM2 pathway.

Traumatic brain injury (TBI) is a severe condition that leads to brain damage and affects brain function. Importantly, TBI incurs public health costs due to its high mortality, and effective treatment for TBI is still lacking. Docosahexaenoic acid (DHA) has a neuroprotective effect that can reduce oxidative, apoptosis, and inflammatory processes. Administration of DHA after TBI attenuates oxidative stress and protein accumulation and is regarded as a potential therapeutic. Iduna is a regulator of parthanatos, and upregulation of Iduna reduces cellular damage and mitochondrial dysfunction. Thus, we speculated that overexpression of Iduna might promote DHA therapy in the treatment of TBI. Here, we found that after combination overexpression of Iduna and DHA in a mouse model of TBI, the expression of inflammatory factors was reduced, while the secretion of neuroprotective factors was increased. In addition, we found that these effects might be mediated by the Wnt/MDM2 pathway, and Iduna might be a therapeutic target for TBI.

Inhibition of ASC enhances the protective role of salvianolic acid A in traumatic brain injury via inhibition of inflammation and recovery of mitochondrial function.

More than 50 million people are affected by traumatic brain injury (TBI) each year around the world, and nearly half of the population worldwide will have one or more TBI(s) in their lifetime. And in 2017, more than 1.39 billion people in China suffered from TBI, representing nearly 18% of the world population; these were mainly caused by road traffic incidents. Salvianolic acid A is a compound obtained from Salvia miltiorrhiza Bunge, which is one of the active components of many traditional Chinese medicines for the treatment of cardiovascular and cerebrovascular disease, with the effect of inhibition of inflammatory response. ASC is a critical factor in the activation of inflammation response process via promoting the maturation of caspase-1, and activation of NLPR3 under bacterial infection promotes the necrosis of cells in an ASC-dependent manner. However, few studies focus on the effect of ASC in a TBI model. In this study, we found that inhibition of ASC reduced the expression of inflammatory cytokines, and the concentration of calcium and ROS, while it increased the expression of mitochondrial function-related proteins. We further noticed that these effects were regulated by DLK2/MLK3/JNK signalling pathway and might contribute to the treatment of TBI.