title: Nonessential Role for the NLRP1 Inflammasome Complex in a Murine Model of Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) elicits the immediate production of proinflammatory cytokines which participate in regulating the immune response. While the mechanisms of adaptive immunity in secondary injury are well characterized, the role of the innate response is unclear. Recently, the NLR inflammasome has been shown to become activated following TBI, causing processing and release of interleukin-1β (IL-1β). The inflammasome is a multiprotein complex consisting of nucleotide-binding domain and leucine-rich repeat containing proteins (NLR), caspase-1, and apoptosis-associated speck-like protein (ASC). ASC is upregulated after TBI and is critical in coupling the proteins during complex formation resulting in IL-1β cleavage. To directly test whether inflammasome activation contributes to acute TBI-induced damage, we assessed IL-1β, IL-18, and IL-6 expression, contusion volume, hippocampal cell death, and motor behavior recovery in Nlrp1(-/-), Asc(-/-), and wild type mice after moderate controlled cortical impact (CCI) injury. Although IL-1β expression is significantly attenuated in the cortex of Nlrp1(-/-) and Asc(-/-) mice following CCI injury, no difference in motor recovery, cell death, or contusion volume is observed compared to wild type. These findings indicate that inflammasome activation does not significantly contribute to acute neural injury in the murine model of moderate CCI injury.
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brickler
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Kisha
authors.initials: K
authors.lastname: Gresham
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Armand
authors.initials: A
authors.lastname: Meza
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Coutermarsh-Ott
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Tere M
authors.initials: TM
authors.lastname: Williams
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Rothschild
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Irving C
authors.initials: IC
authors.lastname: Allen
authors.affiliation: The Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Duck Pond Drive, Blacksburg, VA 24061, USA.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Theus
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000070642:Brain Injuries, Traumatic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000378:metabolism; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; C529636:NALP1 protein, mouse; C498534:Pycard protein, mouse; D020170:Caspase 1