Figure 1.

Our proposed contributory mechanism of IL-1β signaling during a single, brief seizure or mild TBI. Enhanced IL-1β signaling from excitotoxic depolarization results in increased glutamate receptor activity and further propagation of excitotoxic signaling, resulting in an accumulation of post-synaptic glutamate. Increased neuroinflammatory signaling, including upregulated cytokine and Aβ secretion and increased concentrations of extracellular glutamate, recruit microglia and reactive astrocytes to the post-synaptic cleft. Unsuccessful clearance of extracellular glutamate, cellular debris, and Aβ from the synaptic cleft by reactive astrocytes and microglia leads to further excitotoxic propagation and places the cell at risk for excitotoxic injury. Successful clearance, however, reduces the risk of excitotoxic injury, as it attempts to revert the cell to neuronal homeostasis.