The immune response of the human brain to abdominal surgery

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A growing body of evidence suggests that surgical trauma launches a systemic inflammatory response that ultimately reaches and activates the intrinsic immune system of the brain.1 Triggered by surgery‐induced damage‐associated molecular patterns (DAMPs), an array of proinflammatory mediators and activated blood‐borne immune cells orchestrate a rapid spread of this systemic response to the central nervous system (CNS), with inflammatory markers detectable in human cerebrospinal fluid (CSF) within 12 hours.4 In surgical rodent models, this periphery‐to‐brain pathway seems critically dependent on NF‐κB and proinflammatory cytokine signaling (eg, tumor necrosis factor‐α [TNF‐α]) associated with a short‐lasting disruption of blood–brain barrier integrity,2 migration of peripheral macrophages into the CNS, and subsequent hippocampal neuronal dysfunction and cognitive impairment.8 In addition to an acute and transient response, often referred to as a syndrome of sickness behavior including fatigue, anorexia, and fever, surgery‐induced immune activation may be associated with prolonged impairments in learning, memory, and concentration termed postoperative cognitive dysfunction.9
In patients, inflammatory molecules such as TNF‐α and interleukins appear in CSF within 12 hours after major surgery.4 Although such clinical observations are in line with a series of experimental studies,2 the time course pattern beyond the immediate postsurgery phase of immune activation within the human CNS is unknown, and how the systemic pro‐ and anti‐inflammatory response16 is associated with cognitive performance is largely unexplored.
The use of positron emission tomography (PET) and radioligands selective for the translocator protein (TSPO) provide an opportunity for translational studies exploring brain immune activity after surgery. In brain parenchyma, TSPO is primarily expressed in microglia and to a lesser extent in astrocytes. This protein can be viewed as a marker for CNS immune activation, because changes in TSPO levels have been shown to reflect changes in glial cell activity.19 TSPO expression is typically elevated in several acute and chronic CNS disorders involving the immune system21 as well as in animal models of acute inflammation26 or stroke.19 With regard to periphery‐to‐brain interactions, lipopolysaccharide (LPS)‐induced acute systemic inflammation is followed by a rapid and transient activation of the brain immune system, as demonstrated using the TSPO radioligand [11C]PBR28 in nonhuman primates27 and humans.28
Here, we examined the impact of major surgery on the human brain immune system by a longitudinal series of PET examinations of TSPO binding in otherwise healthy patients undergoing abdominal surgery and how changes in glial cell activation relate to systemic inflammatory response and cognitive performance.
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