Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect β-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer’s disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the Aβ plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct β-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.

Background: Simultaneous multipolar ablation catheters have been proposed to simplify

ICE represents a useful technique for the diagnosis of ICM, thus providing improved imaging of right-sided leads and increasing the diagnostic yield compared with TEE.

Objective: Recent data suggest that vagus nerve stimulation (VNS) can inhibit cytokine release by inflammatory cells. Accordingly, an association between impaired cardiac parasympathetic function, as assessed by heart rate variability (HRV), and increased markers of inflammation has recently been reported. In this study we assessed the effect of direct left VNS on inflammatory markers and HRV in patients with refractory epilepsy. Methods: A 24-hour electrocardiogram Holter recording was performed both at baseline and after 3 months of left VNS in 8 patients (age 32 ± 24 years, 2 men) who underwent implantation of a VNS device because of refractory epilepsy. Tumor necrosis factor-α, interleukin-6 and C-reactive protein serum levels were measured, as markers of inflammation, at the same times. Results: No significant changes were found after 3 months of left VNS, compared to baseline, both for HRV variables and inflammatory markers. Also, no consistent correlation could be demonstrated between HRV parameters and inflammatory markers in these patients. Conclusions: Our data in epileptic patients without cardiovascular disease failed to show a significant effect of left VNS on cardiac autonomic function and on systemic inflammation at short-term follow-up.