title: Cerebral Mast Cells Participate In Postoperative Cognitive Dysfunction by Promoting Astrocyte Activation.
abstract: BACKGROUND
  Astrocytes, the major glial cell type that has been increasingly recognized as contributing to neuroinflammation, are critical in the occurrence and development of postoperative cognitive dysfunction (POCD). Although emerging evidence showed that brain mast cells (MCs) are the "first responders" in neuroinflammation, little is known about the functional communication between MCs and astrocytes.
  
  
  METHODS
  In this study, we investigated the potential regulation of astrocyte activation by MCs. Rats received an intracerebroventricular injection of Cromolyn (an MC stabilizer) or sterile saline 30 min before undergoing open tibial fracture surgery, and the levels of neuroinflammation and the degree of memory dysfunction were evaluated at 1 day and 3 days after surgery. In the in vitro study, the effect of activated MCs on astrocytes were further clarified.
  
  
  RESULTS
  Surgery increased the number of MCs, the astrocyte activation and the production of inflammatory factors, and resulted in cognitive deficits. Site-directed pre-injection of Cromolyn can inhibit this effect. In the vitro study, the conditioned medium from C48/80-stimulated mast cells (P815) could induce primary astrocyte activation and subsequent production of inflammatory cytokines, which could be inhibited by Cromolyn.
  
  
  CONCLUSIONS
  These findings indicate that activated MCs could trigger astrocyte activation, be involved in neuroinflammation and possibly contribute to POCD. Interactions between MCs and astrocytes could provide potential therapeutic targets for POCD.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Yao
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Qian
authors.forename: Nana
authors.initials: N
authors.lastname: Li
authors.forename: Wenjie
authors.initials: W
authors.lastname: Jin
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count; D015550:Cell Degranulation / Q000187:drug effects; D054022:Cerebrum / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D011183:Postoperative Complications / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000601:surgery
chemical_list: D016207:Cytokines; D004205:Cromolyn Sodium