title: Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption.
abstract: Trauma induced neuroinflammation plays a key role in the development of postoperative cognitive dysfunction (POCD). The blood-brain barrier (BBB), a highly specialized endothelial layer, is exquisitely sensitive to inflammatory insults, which can result in numerous neurocognitive syndromes. While brain mast cells are the "first responder" in the injury, the functional interactions between mast cells and the BBB remain poorly understood. Our results demonstrate that tibial fracture surgery can induce cognitive impairment relating to an inflammatory response and destabilization of the BBB. Disodium cromoglycate (cromolyn)--which acts as a mast cell stabilizer--inhibited this effect. Specifically, cromolyn resulted in ameliorated cognitive ability, decrease of inflammatory cytokines and increase of BBB stability. Taken together, these results suggest that activated mast cells contributed to central nervous system inflammation and cognitive dysfunction by promoting BBB disruption, and interactions between mast cells and the BBB could constitute a new and unique therapeutic target for POCD.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Susu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Nana
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address: dgsunjie@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China. Electronic address: yanning_qian@163.com.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology; D002491:Central Nervous System Agents / Q000494:pharmacology; D062507:Claudin-5 / Q000378:metabolism; D003072:Cognition Disorders / Q000276:immunology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D011183:Postoperative Complications / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013978:Tibial Fractures / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002491:Central Nervous System Agents; D062507:Claudin-5; C491510:Cldn5 protein, rat; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D062793:Occludin; C568987:Ocln protein, rat; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D004205:Cromolyn Sodium
keywords: Blood-brain barrier; Cognitive; Mast cell; Neuroinflammation; Postoperative cognitive dysfunction