title: Single hind limb burn injury to mice alters nuclear factor-κB expression and [¹⁸F] 2-fluoro-2-deoxy-D-glucose uptake.
abstract: Burn trauma to the extremities can produce marked systemic effects in mice. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism ([18F] 2-fluoro-2-deoxy-D-glucose [18FDG] uptake) by brown adipose tissue (BAT) and nuclear factor (NF)-κB activity in several tissues including skeletal muscle. This study examined the effect of a single hind limb burn in mice on 18FDG uptake by NF-κB activity in vivo, and blood flow was determined by laser Doppler techniques. Male NF-κB luciferase reporter mice (28-30 g) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham-treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 mL, i.p.). The individual animals were placed in wire bottom cages with no food and free access to water. After 24 hours, the animals were imaged with laser Doppler for measuring blood flow in the hind limb. The animals were then unanesthetized with 50 μCi of FDG or luciferin (1.0 mg, i.v.) via tail vein. Five minutes after luciferin injection, NF-κB mice were studied by bioluminescence imaging with a charge-coupled device camera. One hour after 18FDG injection, the animals were killed with carbon dioxide overdose, and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full-thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than that in the contralateral limb. Similarly, luciferase activity and blood flow in the burned leg were lower than those in the contralateral leg. 18FDG uptake by BAT and heart increased, whereas that by brain decreased. In conclusion, the present study suggests that burn injury to a single leg decreased FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression compared with the contralateral leg and the uninjured skeletal muscle of the sham but activated NF-κB expression in a number of other organs. These findings are consistent with the hypothesis that burn trauma to the extremities can produce marked systemic effects, including activation of NF-κB expression and activation of 18FDG uptake by BAT.
authors.affiliation: From the *Department of Pediatrics, Massachusetts General Hospital, Boston; †Shriners Hospitals for Children, Boston, Massachusetts; and Departments of ‡Nuclear Medicine and §Surgery, Massachusetts General Hospital, Boston.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Carter
authors.forename: Victoria
authors.initials: V
authors.lastname: Hamrahi
authors.forename: Kasie
authors.initials: K
authors.lastname: Paul
authors.forename: Ali A
authors.initials: AA
authors.lastname: Bonab
authors.forename: Walter
authors.initials: W
authors.lastname: Jung
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002056:Burns / Q000378:metabolism*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply / Q000293:injuries*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D016328:NF-kappa B; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose
references.citation: J Surg Res. 2003 Mar;110(1):310-4
references.pmid: 12697416
references.citation: Photochem Photobiol Sci. 2004 May;3(5):451-8
references.pmid: 15122362
references.citation: Int J Obes (Lond). 2010 Oct;34 Suppl 1:S36-42
references.pmid: 20935665
references.citation: J Trauma. 1977 May;17(5):344-50
references.pmid: 870699
references.citation: Nat Rev Immunol. 2005 Oct;5(10):749-59
references.pmid: 16175180
references.citation: Life Sci. 2011 Jul 18;89(3-4):78-85
references.pmid: 21565200
references.citation: J Surg Res. 1981 Nov;31(5):404-14
references.pmid: 7029139
references.citation: Am J Physiol. 1986 Feb;250(2 Pt 2):R207-10
references.pmid: 3080903
references.citation: J Trauma. 1988 Aug;28(8):1181-7
references.pmid: 2970556
references.citation: Exp Mol Pathol. 1986 Oct;45(2):185-92
references.pmid: 3770144
references.citation: J Trauma. 1996 Jun;40(6):930-5
references.pmid: 8656479
references.citation: Shock. 2002 Apr;17(4):293-9
references.pmid: 11954829
references.citation: J Burn Care Rehabil. 2000 Mar-Apr;21(2):135-41
references.pmid: 10752746
references.citation: J Nucl Med. 2009 Jun;50(6):966-73
references.pmid: 19443595
references.citation: J Gastrointest Surg. 2002 Mar-Apr;6(2):264-70
references.pmid: 11992813
references.citation: Am J Physiol Endocrinol Metab. 2000 Nov;279(5):E1114-21
references.pmid: 11052967
references.citation: FASEB J. 2002 Apr;16(6):529-38
references.pmid: 11919155
references.citation: Biochem Biophys Res Commun. 2001 Mar;281(5):1331-6
references.pmid: 11243882
references.citation: J Surg Res. 1979 Feb;26(2):171-4
references.pmid: 423570
references.citation: Biochem J. 1984 Nov 1;223(3):747-53
references.pmid: 6508738
references.citation: J Trauma. 1982 Oct;22(10):845-52
references.pmid: 7131603