Fig. 2

SAE acts as a vicious cycle of sepsis-induced immunosuppression. In the physiological condition, the brain is essential for the homeostasis of systemic immune response due to its central role in multiple types of neuroendocrine immune networks, including hypothalamic-pituitary-adrenal (HPA) axis, sympathetic and parasympathetic nervous system, which are capable of inhibiting excessive inflammation and enabling efficient immunomodulation. Appropriate infiltration of immune cells into the central nervous system is beneficial for functional integrity and viability of neurons. However, sepsis-induced immunosuppression contributes to intractable neuroinflammation which results in massive loss of effective nuclei and serious cognitive impairment. Furthermore, persistent brain injury impairs peripheral immune response due to abnormal response of these neuromodulatory mechanisms which present with either significant suppression or unexpected hyperactivity