Figure 1.

Systemic immune responses to trauma. Injured cells release DAMPs, including HMGB1, in response to surgical trauma after being combined with the TLR and RAGE, which can activate nuclear factor-kappa B (NF-κB) signaling pathways in BMDMs, promoting the release of pro-inflammatory cytokines, including IL-6 and TNFα, IL-1. The increased expression of COX-2 and MMPs disrupts the integrity of the blood–brain barrier. Pro-inflammatory cytokines activate microglia to further amplify the release of pro-inflammatory cytokines in the brain. Glia activated by the pro-inflammatory cytokines can further stimulate the release of glutamate. The postsynaptic intracellular Ca²⁺ concentration increases by the overactivation of NMDARs. The ability of astrocytes to clear glutamate is decreased. Figure created with Biorender.com (accessed on 2 March 2022).