Motor units comprise a motoneuron and the muscle fibers it innervates. Neuromuscular transmission is tightly regulated to match the activity of individual motor units. Activity-dependent release of neuromodulators at the neuromuscular junction (NMJ) determines the efficacy of transmission. The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) are produced by motoneurons and muscle fibers, and their release by skeletal muscle is regulated by muscle activity. BDNF and NT-4 enhance both spontaneous and evoked synaptic transmission at NMJs via activation of the tyrosine kinase receptor B (TrkB). Improvements in neuromuscular transmission may result from increased release of synaptic vesicles, either by presynaptic alterations in Ca(2+) transients or facilitated vesicular exocytosis. In fact, BDNF potentiates intracellular Ca(2+) release presynaptically and BDNF-induced TrkB activation also results in phosphorylation of synapsin I via mitogen activated protein kinase, which increases the number of synaptic vesicles available for release. Neurotrophins may also regulate synaptic transmission at the NMJ by increasing local release of neuregulin or other nerve-derived modulators. We review recent studies on the regulation of neuromuscular transmission, the motor unit-specific properties of NMJs and the effects of neurotrophins on synaptic efficacy at the NMJ.
Animals ; Brain-Derived Neurotrophic Factor ; physiology ; Calcium ; metabolism ; Humans ; Nerve Growth Factors ; physiology ; Neuromuscular Junction ; physiology ; Neuronal Plasticity ; Receptor, trkB ; metabolism ; Synapses ; metabolism ; Synapsins ; metabolism ; Synaptic Vesicles

Purpose: Internal carotid artery (ICA) aneurysm treatment with a flow diverter (FD) has shown an adequate efficacy and safety profile, presenting high complete occlusion or near occlusion rates with low complications during follow-up. The purpose of this study was to evaluate the efficacy and safety of FD treatment in non-ruptured internal carotid aneurysms. Materials and Methods: This is a retrospective, single-center, observational study evaluating patients diagnosed with unruptured ICA aneurysms treated with an FD between January 1, 2014, and January 1, 2020. We analyzed an anonymized database. The primary effectiveness endpoint was complete occlusion (O’Kelly–Marotta D, OKM-D) of the target aneurysm through 1-year follow-up. The safety endpoint was the evaluation of modified Rankin Scale (mRS) 90 days after treatment, considering a favorable outcome an mRS 0-2. Results: A total of 106 patients were treated with an FD, 91.5% were women; the mean follow- up was 427.2±144.8 days. Technical success was achieved in 105 cases (99.1%). All patients included had 1-year follow-up digital subtraction angiography control; 78 patients (73.6%) completed the primary efficacy endpoint by achieving total occlusion (OKM-D). Giant aneurysms had a higher risk of not achieving complete occlusion (risk ratio, 3.07; 95% confidence interval, 1.70 - 5.54]). The safety endpoint of mRS 0-2 at 90 days was accomplished in 103 patients (97.2%). Conclusion Treatment of unruptured ICA aneurysms with an FD showed high 1-year total occlusion results, with very low morbidity and mortality complications.