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Neuronal dysfunction leads to Neuroinflammation
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Stressed or injured neurons may decrease their synthesis/release of chemokines maintaining microglial cells in a quiescent state (Blank and Prinz, 2013; Chapman et al., 2000; Streit et al., 2001). Consequently microglial cells are becoming reactive, releasing bio-molecules such as cytokines. The pro-inflammatory cytokine IL-6 is known as an inductor of astrocyte reactivity (Chiang et al., 1994).
Neuronal death can lead to the release of intracellular content acting on microglial cells on specific receptors such as DAMPS (Damage Associated Molecular Pathways) (Marin-Teva et al., 2011)
Evidence Collection Strategy
Evidence Supporting this KER
It is well accepted that under normal physiological conditions, microglial cells participate in surveillance of neuronal integrity (Nimmerjahn et al., 2005), and that in case of neuronal stress, injury or death, microglial cells are becoming reactive, what is the initiation of the neuroinflammatory process.
Uncertainties and Inconsistencies
Following paraquat exposure, it was observed that neuronal dysfunction was observed together with astrocyte reactivity, evidenced by increased expression of glial fibrillary acidic protein (GFAP), whereas microglial reactivity was delayed and occurring despite a partial but important neuronal recovery (Sandström et al., 2014). Such observations suggest that the temporal evolution of the inflammatory process is crucial.
It cannot be excluded that toxicant can affect directly glial cells and induce secondarily neuronal injury.
Cell-cell interactions play a key role in the triggering, evolution and consequences of neuroinflammation.
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
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