Effect of δ-opioid receptor activation on BDNF-TrkB vs. TNF-α in the mouse cortex exposed to prolonged hypoxia.

We investigated whether δ -opioid receptor (DOR)-induced neuroprotection involves the brain-derived neur otrophic factor (BDNF) pathway. We studied the effect of DOR activation on the expression of BDNF and other proteins in the cortex of C57BL/6 mice exposed to hypoxia (10% of oxygen) for 1–10 days. The results showed that: (1) 1-day hypoxia had no appreciable eff ect on BDNF expression, wh ile 3- and 10-day hypoxia progressively decreased BDNF expression, resulting in 37.3% reduction ( p < 0.05) after 10-day exposure; (2) DOR activa tion with UFP-512 (1 mg/kg, i .p., daily) partially reversed the hypoxia-induced reductio n of BDNF expression in the 3- or 10-day exposed cortex; (3) DOR activation partially reversed the hypoxia-induced reduction in functional TrkB (140-kDa) and attenuated hypoxia-indu ced increase in truncated Tr kB (90-kDa) in the 3- or 10-day hypoxic cortex; and (4) prolonged hypoxi a (10 days) significantly increased TNF- α level and decreased CD11b expression in the cortex, which was completely reversed following DOR activation; and (5) there was no significant change in pCREB and pATF-1 levels in the hypoxic cortex. We concl ude that prolonged hypoxia down-regulates BDNF-TrkB signaling leading to an increase in TNF-α in the cortex, while DOR activation up-regulates BDNF-TrkB signaling thereby decreasing TNF-α levels in the hypoxic cortex

Endovascular treatment of complicated versus uncomplicated acute type B aortic dissection

Objective: The study objective was to analyze the outcomes of thoracic endovascular aortic repair performed for complicated and uncomplicated acute type B aortic dissections. Methods: Patients from WL Gore's Global Registry for Endovascular Aortic Treatment who underwent thoracic endovascular aortic repair for acute type B aortic dissections were included, and data were retrospectively analyzed. Results: Of 5014 patients enrolled in the Global Registry for Endovascular Aortic Treatment, 172 underwent thoracic endovascular aortic repair for acute type B aortic dissections. Of these repairs, 102 were for complicated acute type B aortic dissections and 70 were for uncomplicated acute type B aortic dissections. There were 46 (45.1%) procedures related to aortic branch vessels versus 15 (21.4%) in complicated type B aortic dissections and uncomplicated type B aortic dissections (P = .002). The mean length of stay was 14.3 ± 10.6 days (median, 11; range, 2-75) versus 9.8 ± 7.9 days (median, 8; range, 0-42) in those with complicated type B aortic dissections versus those with uncomplicated acute type B aortic dissections (P &lt; .001). Thirty-day mortality was not different between groups (complicated type B aortic dissections 2.9% vs uncomplicated acute type B aortic dissections 1.4%, P = .647), as well as aortic complications (8.8% vs 5.7%, P = .449). Aortic event-free survival was 62.9% ± 37.1% versus 70.6% ± 29.3% at 3 years (P = .696). Conclusions: In the Global Registry for Endovascular Aortic Treatment, thoracic endovascular aortic repair results for complicated type B aortic dissections versus uncomplicated acute type B aortic dissections showed that 30-day mortality and perioperative complications were equally low for both. The midterm outcome was positive. These data confirm that thoracic endovascular aortic repair as the first-line strategy for treating complicated type B dissections is associated with a low risk of complications. Further studies with longer follow-up are necessary to define the role of thoracic endovascular aortic repair in uncomplicated acute type B dissections compared with medical therapy. However, in the absence of level A evidence from randomized trials, results of the uncomplicated acute type B aortic dissection patient cohort treated with thoracic endovascular aortic repair from registries are important to understand the related risk and benefit