Anti-inflammatory effects induced by pharmaceutical substances on inflammatory active brain astrocytes—promising treatment of neuroinflammation

摘要

BackgroundPharmaceutical treatment with probable anti-inflammatory substances that attack cells in various ways including receptors, ion channels, or transporter systems may slow down the progression of inflammatory conditions. Astrocytes and microglia are the most prominent target cells for inflammation in the central nervous system. Their responses upon inflammatory stimuli work through the NO/cyclic GMP/protein kinase G systems that can downregulate the ATP-induced Ca²⁺ signaling, as well as G protein activities which alter Na⁺ transporters including Na⁺/K⁺-ATPase pump activity, Toll-like receptor 4 (TLR4), glutamate-induced Ca²⁺ signaling, and release of pro-inflammatory cytokines. The rationale for this project was to investigate a combination of pharmaceutical substances influencing the NO and the Gi/Gs activations of inflammatory reactive cells in order to make the cells return into a more physiological state. The ATP-evoked Ca²⁺ signaling is important maybe due to increased ATP release and subsequent activation of purinergic receptors. A balance between intercellular Ca²⁺ signaling through gap junctions and extracellular signaling mediated by extracellular ATP may be important for physiological function.