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Published on: March 5, 2018
Complement activation contributes to perioperative neurocognitive disorders in mice.
Chao Xiong1, Jinhu Liu2, Dandan Lin1
1Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Orthopedic surgery activates complement C3a receptor signaling, contributing to neuroinflammation and cognitive decline. Blocking this pathway may offer a therapeutic strategy for perioperative neurocognitive disorders (PND).
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- The complement system, particularly C3/C3a receptor signaling, is implicated in neurological disorders and shows therapeutic potential for cognition.
- The role of complement signaling in perioperative neurocognitive disorders (PND) remains unclear.
- This study investigates the C3/C3a receptor pathway's involvement in PND following orthopedic surgery.
Purpose of the Study:
- To evaluate the role of C3/C3a receptor signaling in a mouse model of PND after orthopedic surgery.
- To assess the therapeutic potential of C3a receptor blockade in mitigating PND-related deficits.
Main Methods:
- Adult male mice underwent tibial fracture surgery to induce PND-like behavior.
- Complement activation, neuroinflammation, synapse integrity, blood-cerebrospinal fluid barrier (BCSFB) function, and memory were assessed.
- Mice were treated with a C3a receptor blocker.
Main Results:
- Surgery increased C3 levels and C3a receptor expression in the hippocampus.
- C3a receptor blockade attenuated surgery-induced neuroinflammation, synapse loss, and BCSFB dysfunction.
- C3a receptor blockade improved memory function, while C3a administration worsened cognitive decline.
Conclusions:
- Orthopedic surgery activates complement C3a receptor signaling.
- C3a receptor blockade demonstrates therapeutic potential for reducing neuroinflammation and improving cognitive function in PND.
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