Journal of neuroinflammation, 2018-09, Vol.15 (1), p.254-13, Article 254
2018
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- Autor(en) / Beteiligte
- Titel
- Complement activation contributes to perioperative neurocognitive disorders in mice
- Ist Teil von
- Journal of neuroinflammation, 2018-09, Vol.15 (1), p.254-13, Article 254
- Ort / Verlag
- England: BioMed Central Ltd
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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. 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. Orthopedic surgery activates complement signaling. C3a receptor blockade may be therapeutically beneficial to attenuate neuroinflammation and PND.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1742-2094eISSN: 1742-2094DOI: 10.1186/s12974-018-1292-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_2548a818338d4ae7ac83317b5be99789
- Format
- –
- Schlagworte
- Alzheimer's disease, Analgesia, Anesthesia, Anesthesiology, Animals, Astrocytes, Astrocytes - drug effects, Astrocytes - metabolism, Blood-Brain Barrier - physiopathology, Bone marrow, Bone surgery, Cellular signal transduction, Cerebrospinal fluid, Choroid plexus, Choroid Plexus - metabolism, Cognition, Cognition disorders, Cognitive ability, Complement, Complement activation, Complement Activation - drug effects, Complement Activation - physiology, Complement component C3, Complement component C3a, Complement Factor I - pharmacology, Complement receptors, Complement System Proteins - metabolism, Conditioning, Classical - drug effects, Conditioning, Classical - physiology, Cytophagocytosis - drug effects, Disease Models, Animal, Fear - psychology, Fractures, Hippocampus, Hippocampus - metabolism, Hippocampus - pathology, Inflammation, Male, Memory, Mice, Mice, Inbred C57BL, Microglia, Microglia - drug effects, Microglia - metabolism, Neurocognitive Disorders - drug therapy, Neurocognitive Disorders - etiology, Neurocognitive Disorders - metabolism, Neurocognitive Disorders - pathology, Neurodegeneration, Neuroinflammation, Neurological diseases, Neuromodulation, Orthopedics, Pain perception, Pathogenesis, Perioperative neurocognitive disorders, Postoperative Complications - drug therapy, Postoperative Complications - physiopathology, Rats as laboratory animals, Regulation, Rodents, Signal Transduction - drug effects, Signal Transduction - physiology, Surgery, Synapses - drug effects, Synapses - pathology, Tibial Fractures - surgery, Up-Regulation - drug effects, Up-Regulation - physiology