title: Antagonism of the interleukin-1 receptor following traumatic brain injury in the mouse reduces the number of nitric oxide synthase-2-positive cells and improves anatomical and functional outcomes.
abstract: Interleukin (IL)-1beta plays an important role in the inflammatory response that results from traumatic brain injury and antagonism of the actions of this cytokine can affect outcome. We subjected male mice to aseptic cryogenic injury and assessed recovery through anatomical, histological and functional measures following treatment with recombinant mouse IL-1 receptor antagonist (IL-1ra). A single dose (1 microg, i.c.v.) at the time of injury reduced lesion volume 3 days later, as assessed by Nissl staining, and also the number (30%) of FluoroJade-positive degenerating neurones. Mice treated with IL-1ra performed better on the beam balance and in the grid test as compared with vehicle-treated animals. Furthermore, IL-1ra-treated animals showed fewer (40%) nitric oxide synthase-2-positive cells in and around the lesion. These data suggest that activation of the IL-1 receptor following trauma contributes to the pathology and that antagonism can reduce both anatomical and functional consequences of neuroinflammation.
authors: Institute of Cell Signalling, University of Nottingham, Clifton Boulevard, Nottingham NG7 2UH, UK.
authors: Nigel C
authors: NC
authors: Jones
authors: Malcolm J W
authors: MJ
authors: Prior
authors: Esther
authors: E
authors: Burden-Teh
authors: Charles A
authors: CA
authors: Marsden
authors: Peter G
authors: PG
authors: Morris
authors: Sean
authors: S
authors: Murphy
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C507764:Il1rn protein, mouse; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D018696:Neuroprotective Agents; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse