L

Nowadays, amyotrophic lateral sclerosis (ALS) is considered as a multisystem disorder, characterized by a primary degeneration of motor neurons as well as neuropathological changes in non-motor regions. Neurodegeneration in subcortical areas, such as the thalamus, are believed to contribute to cognitive and behavioral abnormalities in ALS patients. In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS. We detected massive dendrite swelling and neuronal loss in SOD1(G93A) animals, which was accompanied by a mild gliosis. Furthermore, misfolded SOD1 protein and autophagy markers were accumulating in the AD. Since innate immunity and activation inflammasomes seem to play a crucial role in ALS, we examined protein expression of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) and the cytokine interleukin 1 beta (IL1β) in AD glial cells and neurons. NLRP3 and ASC were significantly up-regulated in the AD of SOD1(G93A) mice. Finally, co-localization studies revealed expression of NLRP3, ASC and IL1β in neurons. Our study yielded two main findings: (i) neurodegenerative changes already occur at an early symptomatic stage in the AD and (ii) increased inflammasome expression may contribute to neuronal cell death. In conclusion, neurodegeneration in the anterior thalamus may critically account for cognitive changes in ALS pathology.

Growing interest in regenerative medicine and advances in adipose tissue research have led to the identification of mesenchymal stem cells in adipose tissue, so called adipose tissue-derived stem cells (ASCs). Due to the simple and safe harvest technique as well as high regenerative capacity, ASCs are regarded as a potential source for various indications including cutaneous wound repair. This review provides a short overview over mechanisms of ASC action in cutaneous wound repair and data regarding its clinical application. Mostly experimental data provide accruing evidence for the supportive effect of ASCs in cutaneous wound healing by secretion of soluble factors, differentiation into keratinocyte and fibroblasts, neovascularization and interaction with myofibroblasts. A number of in vivo experiments also support a positive effect of ASCs in different wound healing models. Furthermore, first clinical data evaluated the feasibility of ASCs in the treatment of different wound healing pathologies, e.g., chronic ulcers and burn wounds. Although the majority of currently available data indicate a beneficial role of ASCs in cutaneous wound repair, additional detailed experimental studies and larger, high-quality clinical trials are required to provide a reliable statement on the true value of ASCs in this context.