Brain-Region-Mediated Neuroimmune Modulation in Sepsis: Research Advances and Therapeutic Prospects

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, lacks effective treatments targeting its pervasive immune dysregulation. Despite growing interest in neuroimmune interactions, there remains a fragmented understanding of how distinct brain regions integrate peripheral immune signals and orchestrate systemic immune responses in sepsis. Emerging evidence highlights the brain as a master regulator of systemic immunity in sepsis through the neuro-immune-endocrine network. This review summarizes recent advances in understanding how distinct brain regions, including the hypothalamus, brainstem, cortex and cerebellum, sense peripheral inflammation and feedback-regulate systemic immune responses via dedicated neural circuits, neurotransmitters, and autonomic outputs. We also highlight the therapeutic potential of neuromodulation techniques designed to target these central circuits and discuss their implications for developing future precision medicine strategies in sepsis management.