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Complement activation contributes to perioperative neurocognitive disorders in mice.

Publication ,  Journal Article
Xiong, C; Liu, J; Lin, D; Zhang, J; Terrando, N; Wu, A
Published in: J Neuroinflammation
September 4, 2018

BACKGROUND: The complement system plays an important role in many neurological disorders. Complement modulation, including C3/C3a receptor signaling, shows promising therapeutic effects on cognition and neurodegeneration. Yet, the implications for this pathway in perioperative neurocognitive disorders (PND) are not well established. Here, we evaluated the possible role for C3/C3a receptor signaling after orthopedic surgery using an established mouse model of PND. METHODS: A stabilized tibial fracture surgery was performed in adult male C57BL/6 mice under general anesthesia and analgesia to induce PND-like behavior. Complement activation was assessed in the hippocampus and choroid plexus. Changes in hippocampal neuroinflammation, synapse numbers, choroidal blood-cerebrospinal fluid barrier (BCSFB) integrity, and hippocampal-dependent memory function were evaluated after surgery and treatment with a C3a receptor blocker. RESULTS: C3 levels and C3a receptor expression were specifically increased in hippocampal astrocytes and microglia after surgery. Surgery-induced neuroinflammation and synapse loss in the hippocampus were attenuated by C3a receptor blockade. Choroidal BCSFB dysfunction occurred 1 day after surgery and was attenuated by C3a receptor blockade. Administration of exogenous C3a exacerbated cognitive decline after surgery, whereas C3a receptor blockade improved hippocampal-dependent memory function. CONCLUSIONS: Orthopedic surgery activates complement signaling. C3a receptor blockade may be therapeutically beneficial to attenuate neuroinflammation and PND.

Duke Scholars

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Published In

J Neuroinflammation

DOI

EISSN

1742-2094

Publication Date

September 4, 2018

Volume

15

Issue

1

Start / End Page

254

Location

England

Related Subject Headings

  • Up-Regulation
  • Tibial Fractures
  • Synapses
  • Signal Transduction
  • Postoperative Complications
  • Neurology & Neurosurgery
  • Neurocognitive Disorders
  • Microglia
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Xiong, C., Liu, J., Lin, D., Zhang, J., Terrando, N., & Wu, A. (2018). Complement activation contributes to perioperative neurocognitive disorders in mice. J Neuroinflammation, 15(1), 254. https://doi.org/10.1186/s12974-018-1292-4
Xiong, Chao, Jinhu Liu, Dandan Lin, Juxia Zhang, Niccolò Terrando, and Anshi Wu. “Complement activation contributes to perioperative neurocognitive disorders in mice.J Neuroinflammation 15, no. 1 (September 4, 2018): 254. https://doi.org/10.1186/s12974-018-1292-4.
Xiong C, Liu J, Lin D, Zhang J, Terrando N, Wu A. Complement activation contributes to perioperative neurocognitive disorders in mice. J Neuroinflammation. 2018 Sep 4;15(1):254.
Xiong, Chao, et al. “Complement activation contributes to perioperative neurocognitive disorders in mice.J Neuroinflammation, vol. 15, no. 1, Sept. 2018, p. 254. Pubmed, doi:10.1186/s12974-018-1292-4.
Xiong C, Liu J, Lin D, Zhang J, Terrando N, Wu A. Complement activation contributes to perioperative neurocognitive disorders in mice. J Neuroinflammation. 2018 Sep 4;15(1):254.

Published In

J Neuroinflammation

DOI

EISSN

1742-2094

Publication Date

September 4, 2018

Volume

15

Issue

1

Start / End Page

254

Location

England

Related Subject Headings

  • Up-Regulation
  • Tibial Fractures
  • Synapses
  • Signal Transduction
  • Postoperative Complications
  • Neurology & Neurosurgery
  • Neurocognitive Disorders
  • Microglia
  • Mice, Inbred C57BL
  • Mice