Triggers of cellular state transitions in the central nervous system.
| Trigger category | Example molecules/signals | Source | Cellular targets | Functional consequence |
|---|---|---|---|---|
| Damage-associated molecular patterns (DAMPs) | HMGB1, extracellular ATP, extracellular DNA fragments, heat-shock proteins | Injured neurons, damaged glial cells, mitochondrial damage, extracellular matrix breakdown | Microglia, astrocytes, endothelial cells | Activation of pattern-recognition receptors, induction of inflammatory signaling, initiation of neuroimmune responses [77, 78] |
| Pro-inflammatory cytokines | IL-1β, TNF, IL-6, IFN-γ | Microglia, astrocytes, endothelial cells, infiltrating immune cells | Microglia, astrocytes, neurons, immune cells | Activation of inflammatory signaling pathways, modulation of gene-expression programs, promotion of cellular activation states [79, 80] |
| Chemokines | CCL2, CXCL10, CX3CL1 and related chemokines | Activated glial cells, endothelial cells, infiltrating immune cells | Microglia, monocytes/macrophages, T cells | Regulation of immune-cell recruitment, migration, and positioning within neural tissue [81] |
| Metabolic stress signals | Altered glucose metabolism, mitochondrial dysfunction, lipid metabolism shifts | Neurons, glial cells experiencing metabolic imbalance | Microglia, astrocytes, neural stem cells | Activation of immunometabolic pathways and modulation of inflammatory signaling [82, 83] |
| Oxidative stress | Reactive oxygen species, mitochondrial oxidative products | Mitochondrial dysfunction, inflammatory signaling, cellular injury | Neurons, microglia, astrocytes | Modification of signaling proteins, activation of inflammatory transcriptional pathways, amplification of immune responses [84, 85] |
| Hypoxia | Reduced oxygen availability, hypoxia-inducible signaling pathways | Ischemia, vascular dysfunction, tissue injury | Microglia, astrocytes, endothelial cells | Activation of hypoxia-responsive transcription programs and metabolic adaptation pathways [86, 87] |
MMN: Conceptualization, Methodology, Investigation, Resources, Data curation, Formal analysis, Visualization, Writing—original draft, Writing—review & editing. The author read and approved the submitted version.
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