Device-Associated Sepsis and Brain Injury: Transitioning From Early Infection Control to Late Neuroprotection

Sepsis-associated encephalopathy (SAE) is a complex neuroinflammatory condition characterized by diffuse brain dysfunction arising from systemic infection without direct central nervous system invasion. In modern critical care, device-associated infections (DAIs) caused by invasive medical devices, such as central line-associated bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections, have become critical drivers of intensive care unit (ICU)-acquired sepsis. Biofilm formation on these devices establishes persistent inflammatory reservoirs that continuously shed microorganisms, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs) into the circulation, sustaining systemic immune activation. This review outlines an integrated mechanistic framework linking DAIs to acute brain dysfunction. Systemic inflammation and endothelial activation trigger microvascular dysfunction, impaired cerebral autoregulation, and blood-brain barrier disruption. These peripheral vascular alterations allow inflammatory mediators to access the central nervous system, where they induce microglial and astrocytic reactivity. Persistent neuroimmune activation compromises neurotransmitter homeostasis-causing glutamate excitotoxicity and cholinergic deficits-while impairing neuronal mitochondrial oxidative phosphorylation. The resulting oxidative stress, energy failure, and self-amplifying neuroinflammatory feedback loops culminate in synaptic damage and neuronal injury. Clinically, this manifests as altered consciousness, delirium, seizures, and long-term neurocognitive impairment. By framing SAE as a concurrent, multidimensional continuum rather than a linear sequence, this review highlights the critical role of early infection prevention, timely device removal, and targeted neuroprotective strategies aimed at stabilizing vascular integrity and mitigating neuroinflammation.