Figure 8.

Model for cachexia-induced changes in the MBH. Tumor-derived factors cause local stress on endothelial cells affecting many features of endothelial functioning such as expression of adhesion molecules and transmembrane molecules, as well as loosening of the BBB. Tanycytes, which line the ventricle walls, increase expression of metallothioneins. Microglia may either be protective or neurotoxic and Ccr1⁺ macrophages are enriched in the cachectic MBH. The altered state of the BBB affects other cell types such as the oligodendrocytes, which upregulate stress and adhesion molecules. LCN2 activates many features of the immune system, but also other cell types are affected. The combined actions of these cell types ultimately influences neuronal functioning, which display disturbed expression of genes involved in food intake.