title: Expression of the NLRP3 inflammasome in cerebral cortex after traumatic brain injury in a rat model.
abstract: Inflammatory response plays an important role in the pathogenesis of secondary damage after traumatic brain injury (TBI). The inflammasome is a multiprotein complex involved in innate immunity and a number of studies have suggested that the inflammasome plays a critical role in a host inflammatory signaling. Nucleotide-binding domain, leucine-rich repeat, pyrin domain containing 3 (NLRP3) is a key component of the NLRP3-inflammasome, which also includes apoptotic speck-containing protein (ASC) with a cysteine protease (caspase)-activating recruitment domain and pro-caspase1. Activation of the NLRP3-inflammasome causes the processing and release of the interleukin 1 beta (IL-1β) and interleukin 18 (IL-18). Based on this, we hypothesized that the NLRP3-inflammasome could participate in the inflammatory response following TBI. However, the expression of NLRP3-inflammasome in cerebral cortex after TBI is not well known. Rats were randomly divided into control, sham and TBI groups (including 6 h, 1 day, 3 day and 7 day sub-group). TBI model was induced, and animals were sacrificed at each time point respectively. The expression of NLRP3-inflammasome was measured by quantitative real-time polymerase chain reaction, western blot and immunohistochemistry respectively. Immunofluorescent double labeling was performed to identify the cell types of NLRP3-inflammasome's expression. Moreover, enzyme linked immunosorbent assay was used to detect the alterations of IL-1β and IL-18 at each time point post-injury. The results showed that, TBI could induce assembly of NLRP3-inflammasome complex, increased expression of ASC, activation of caspase1, and processing of IL-1β and IL-18. These results suggested that NLRP3-inflammasome might play an important role in the inflammation induced by TBI and could be a target for TBI therapy.
authors.affiliation: Department of Neurosurgery, School of Medicine, Jinling Hospital, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.
authors.forename: Huan-Dong
authors.initials: HD
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zhen-Rui
authors.initials: ZR
authors.lastname: Chen
authors.forename: Yang-Chun
authors.initials: YC
authors.lastname: Hu
authors.forename: Ding-Ding
authors.initials: DD
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001930:Brain Injuries / Q000276:immunology / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D020170:Caspase 1 / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D007113:Immunity, Innate; D058847:Inflammasomes / Q000096:biosynthesis*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; C498535:Pycard protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D020170:Caspase 1
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