Microglia-the brain's primary immune cells-exert a tightly regulated cascade of proand anti-inflammatory effects upon brain pathology, either promoting regeneration or neurodegeneration. Therefore, harnessing microglia emerges as a potential therapeutic concept in neurological research. Recent studies suggest that-besides being affected by chemokines and cytokines-various cell entities in the brain relevantly respond to the mechanical properties of their microenvironment. For example, we lately reported considerable effects of elasticity on neural stem cells, regarding quiescence and differentiation potential. However, the effects of elasticity on microglia remain to be explored.Under the hypothesis that the elasticity of the microenvironment affects key characteristics and functions of microglia, we established an in vitro model of primary rat microglia grown in a polydimethylsiloxane (PDMS) elastomer-based cell culture system. This way, we simulated the brain's physiological elasticity range and compared it to supraphysiological stiffer PDMS controls. We assessed functional parameters of microglia under "resting" conditions, as well as when polarized towards a pro-inflammatory phenotype (M1) by lipopolysaccharide (LPS), or an anti-inflammatory phenotype (M2) by interleukin-4 (IL-4). Microglia viability was unimpaired on soft substrates, but we found various significant effects with a more than twofold increase in microglia proliferation on soft substrate elasticities mimicking the brain (relative to PDMS controls). Furthermore, soft substrates promoted the expression of the activation marker vimentin in microglia. Moreover, the M2-marker CD206 was upregulated in parallel to an increase in the secretion of Insulin-Like Growth Factor-1 (IGF-1). The upregulation of CD206 was abolished by blockage of stretch-dependent chloride channels. Our data suggest that the cultivation of microglia on substrates of brain-like elasticity promotes a basic anti-inflammatory activation state via stretch-dependent chloride

Although—considering the risk–benefit ratio—botulinum neurotoxin A (BoNT/A) is unequivocally recommended to treat severe neurological diseases such as dystonia, this has not yet been determined for its endoscopic intragastric injection aimed at weight reduction in obesity. However, severe adverse effects of intragastric BoNT/A had not yet been reported, prompting some European countries to endorse its (off‐label) use and treat patients transnationally. We here present three cases of botulism after intragastric BoNT/A injections for obesity treatment in a Turkish hospital. Patients presented with cranial nerve affection, bulbar symptoms, and descending paresis, and benefited from treatment with BoNT antitoxin and pyridostigmine. We assume that iatrogenic botulism was induced by overdosing in combination with toxin spread via the highly vascularized gastric tissue. Of note, within a few weeks, more than 80 cases of iatrogenic botulism were reported across Europe after identical intragastric BoNT/A injections. These cases demonstrate the risks of BoNT/A injections if they are not applied within the limits of evidence‐based medicine. There is a need for international guidelines to define the indication and a safe dosing scheme, especially in the context of medical tourism.