RESUMO
BACKGROUND: Giant fusiform dolichoectatic vertebrobasilar artery aneurysms are challenging lesions with a poor natural history. When there is progressive brainstem compression from these lesions, endovascular treatment can be insufficient, and bypass surgery remains a possible salvage option. High-flow bypass surgery with proximal occlusion can potentially arrest aneurysm growth, promote aneurysm thrombosis, and reduce rupture risk. The authors describe their experience in two patients with giant fusiform dolichoectatic vertebrobasilar artery aneurysms treated with high-flow bypass. OBSERVATIONS: Both patients presented with enlarging giant dolichoectatic vertebrobasilar aneurysms causing symptomatic brainstem compression. The authors performed staged treatment involving high-flow bypass from the external carotid artery to the posterior cerebral artery using a saphenous vein graft, Hunterian proximal vertebrobasilar occlusion, and finally posterior fossa decompression with or without direct aneurysm thrombectomy and debulking. Postoperative angiography revealed successful flow reversal, aneurysm exclusion, and no brainstem stroke. Clinically, one patient had improvement in their modified Rankin Scale (mRS) score from 3 preoperatively to 1 at 12-month follow-up. The second patient had a deterioration in their mRS score from 4 to 5 at 12-month follow-up. LESSONS: High-flow bypass strategies remain high risk but can be a viable last resort in patients with neurological deficits and enlarging giant fusiform dolichoectatic vertebrobasilar artery aneurysms.
RESUMO
Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT. Serotonin decreases uncoupled respiration and reduces uncoupling protein 1 via the 5-HT2B receptor. SERT inhibition by the selective serotonin reuptake inhibitor (SSRI) sertraline prevents uptake of extracellular serotonin, thereby potentiating serotonin's suppressive effect on brown adipocytes. Furthermore, we see that sertraline reduces BAT activation in healthy volunteers, and SSRI-treated patients demonstrate no 18F-fluorodeoxyglucose uptake by BAT at room temperature, unlike matched controls. Inhibition of BAT thermogenesis may contribute to SSRI-induced weight gain and metabolic dysfunction, and reducing peripheral serotonin action may be an approach to treat obesity and metabolic disease.
