Formyl peptide receptor 1 is involved in surgery-induced neuroinflammation and dysfunction of learning and memory in...

Postoperative cognitive dysfunction (POCD) is a common complication after surgery. Peripheral immune cells may contribute to the development of POCD. However, molecules that are important for this contribution are not known. We hypothesize that formyl peptide receptor 1 (FPR1), a molecule critical for the migration of the monocytes and neutrophils into the brain after brain ischemia, is central to the development of postoperative neuroinflammation and dysfunction of learning and memory. Male C57BL/6 (wild-type) mice and FPR1^-/- mice received right carotid artery exposure surgery. Some wild-type mice received cFLFLF, an FPR1 antagonist. Mouse brains were harvested 24 h after the surgery for biochemical analysis. Mice were subjected to the Barnes maze and fear conditioning tests to determine their learning and memory from 2 weeks after the surgery. We found that surgery increased FPR1 in the brain and proinflammatory cytokines in the blood and brain of wild-type mice. Surgery also impaired their learning and memory. cFLFLF attenuated these effects. Surgery did not induce an increase in the proinflammatory cytokines and impairment of learning and memory in FPR1^-/- mice. These results suggest that FPR1 is important for the development of neuroinflammation and dysfunction of learning and memory after surgery. Specific interventions that inhibit FPR1 may be developed to reduce POCD.