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. 2025 Nov 21;16:1694003. doi: 10.3389/fimmu.2025.1694003

Figure 2.

Flowchart illustrating the effects of sepsis on the brain, starting with neutrophil and macrophage activation. Cytokines like TNF-α, IL-1β, and IL-6 lead to blood-brain barrier dysfunction, ischemia, hypoxia, axonal injury, and neuronal death. This results in microglial activation, neuroinflammation, brain dysfunction, SAE (Sepsis-Associated Encephalopathy), and potential long-term neurological sequelae. Arrows indicate processes of promotion and inhibition, with neurotransmitters depicted in synaptic transmission.

Key pathophysiological mechanisms of sepsis-related CNS injury. Sepsis activates immune cells, leading to systemic inflammation and damage to the BBB. This disruption allows inflammation into the brain, causing cerebral ischemia and hypoxia. Activated microglia release pro-inflammatory factors, resulting in neuroinflammation, axonal damage, neuronal death, and impaired neurotransmitter transmission, which contributes to brain dysfunction and SAE. Over time, survivors may experience long-term neurological sequelae. Furthermore, neuronal death can worsen neuroinflammation and brain dysfunction in a reciprocal manner.