Effects of thoracic sympathetic stimulation on palmar perfusion: a preliminary study in pigs.

OBJECTIVE: Ablation of the upper thoracic sympathetic ganglia that innervates the hands is the most effective and permanent cure of palmar hyperhidrosis. However, this type of sympathectomy causes irreversible neural damage and may result in severe compensatory hyperhidrosis. This experiment is designed to confirm the hypothesis, in which the stimulation of T2 sympathetic chain leads to increased palmar microcirculation, and thus results in treating hyperhidrosis. METHODS: In this study, we used electric stimulation to induce reversible blockade of the sympathetic ganglion in pigs and investigated its effect on palmar perfusion. An electrode was inserted to the T2 sympathetic ganglion of the pig through three different approaches: open dorsal, thoracoscopic, and fluoroscopy-guided approaches. Electric stimulation was delivered through the electrode using clinically available pulse generators. Palmar microcirculation was evaluated by laser speckle contrast imaging. RESULTS: The T2 sympathetic ganglion of the pig was successfully accessed by all the three approaches, as confirmed by changes in palmar microcirculation during electric stimulation. Similar effects were not observed when the electrode was placed on the T4 sympathetic ganglion or off the sympathetic trunk. CONCLUSION: We established a large animal model to verify the effect of thoracic sympathetic stimulation. Electric stimulation can be used for sympathetic blockade, as confirmed by increased blood perfusion of the palm. Our work suggests that sympathetic stimulation is a potential solution for palmar hyperhidrosis.

Glycogen synthase kinase 3 beta in somites plays a role during the angiogenesis of zebrafish embryos.

Glycogen synthase kinase 3 beta (Gsk3b) acts as a negative modulator in endothelial cells through the Wnt/ß-catenin/PI3K/AKT/Gsk3b axis in cancer-induced angiogenesis. However, the function of Gsk3b during embryonic angiogenesis remains unclear. Here, either gsk3b knockdown by morpholino or Gsk3b loss of activity by LiCl treatment had serious phenotypic consequences, such as defects in the positioning and patterning of intersegmental blood vessels and reduction of vegfaa121 and vegfaa165 transcripts. In embryos treated with the phosphatidylinositol 3-kinase inhibitor, angiogenesis was severely inhibited, along with reduced Wnt, phosphorylated AKT and phosphorylated Gsk3b, suggesting that the remaining Gsk3b in somites could still degrade ß-catenin, resulting in decreased vascular endothelial growth factor Aa(VegfAa) expression. However, in gsk3b-mRNA-overexpressed embryos, intersegmental vessels ectopically sprouted by the increase in phosphorylated-Gsk3b which prevented the degradation of ß-catenin and promoted the increase in phosphorylated AKT activity, thus increasing VegfAa expression in somites. Interestingly, the Gsk3b-dependent cross-talk between PI3K/AKT and Wnt/ß-catenin suggests that Wnt/ß-catenin and PI3K/AKT interaction controls embryonic angiogenesis by a positive feedback loop rather than a hierarchical framework such as that found in cancer-induced angiogenesis. Thus, both active and inactive forms of Gsk3b mediate the cooperative signaling between Wnt/ß-catenin and PI3K/AKT to control VegfAa expression in somites during angiogenesis in zebrafish embryos.

MiR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos.

As miR-1 and miR-206 share identical seed sequences, they are commonly speculated to target the same gene. Here, we identify an mRNA encoding seryl-tRNA synthetase (SARS), which is targeted by miR-1, but refractory to miR-206. SARS is increased in miR-1-knockdown embryos, but it remains unchanged in the miR-206 knockdown. Either miR-1 knockdown or sars overexpression results in a failure to develop some blood vessels and a decrease in vascular endothelial growth factor Aa (VegfAa) expression. In contrast, sars knockdown leads to an increase of VegfAa expression and abnormal branching of vessels, similar to the phenotypes of vegfaa-overexpressed embryos, suggesting that miR-1 induces angiogenesis by repressing SARS. Unlike the few endothelial cells observed in the miR-1-knockdown embryos, knockdown of miR-206 leads to abnormal branching of vessels accompanied by an increase in endothelial cells and VegfAa. Therefore, we propose that miR-1 and miR-206 target different genes and thus have opposing roles during embryonic angiogenesis in zebrafish.