title: β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, and inflammatory response after traumatic brain injury.
abstract: BACKGROUND
  The purpose of this study was to evaluate how β-adrenergic receptor inhibition after traumatic brain injury (TBI) alters changes in early cerebral glucose metabolism and motor performance, as well as cerebral cytokine and heat shock protein (HSP) expression.
  
  
  METHODS
  Mouse cerebral glucose metabolism was measured by microPET fluorodeoxyglucose uptake and converted into standardized uptake values (SUV). Four groups of C57/Bl6 mice (wild type [WT]) were initially evaluated: sham or TBI, followed by tail vein injection of either saline or a nonselective β-adrenergic receptor inhibitor (propranolol, 4 mg/kg). Then motor performance, cerebral cytokine, and HSP70 expression were studied at 12 hours and 24 hours after sham injury or TBI in WT mice treated with saline or propranolol and in β1-adrenergic/β2-adrenergic receptor knockout (BARKO) mice treated with saline.
  
  
  RESULTS
  Cerebral glucose metabolism was significantly reduced after TBI (mean SUV TBI, 1.63 vs. sham 1.97, p < 0.01) and propranolol attenuated this reduction (mean SUV propranolol, 1.89 vs. saline 1.63, p < 0.01). Both propranolol and BARKO reduced motor deficits at 24 hours after injury, but only BARKO had an effect at 12 hours after injury. TBI WT mice treated with saline performed worse than propranolol mice at 24 hours after injury on rotarod (23 vs. 44 seconds, p < 0.01) and rearing (130 vs. 338 events, p = 0.01) results. At 24 hours after injury, sham BARKO and TBI BARKO mice were similar on rotarod (21 vs. 19 seconds, p = 0.53), ambulatory testing (2,891 vs. 2,274 events, p = 0.14), and rearing (129 vs. 64 events, p = 0.09) results. Interleukin 1β expression was affected by BARKO and propranolol after TBI; attenuation of interleukin 6 and increased HSP70 expression were noted only with BARKO.
  
  
  CONCLUSIONS
  β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, as well as cerebral cytokine and HSP expression after TBI.
authors: Department of Surgery, Cedars-Sinai Medical Center, University of Southern California, Los Angeles, CA, USA. eric.ley@cshs.org
authors: Eric J
authors: EJ
authors: Ley
authors: Morgan A
authors: MA
authors: Clond
authors: Marko
authors: M
authors: Bukur
authors: Ryan
authors: R
authors: Park
authors: Michael
authors: M
authors: Chervonski
authors: Grant
authors: G
authors: Dagliyan
authors: Dan R
authors: DR
authors: Margulies
authors: Patrick D
authors: PD
authors: Lyden
authors: Peter S
authors: PS
authors: Conti
authors: Ali
authors: A
authors: Salim
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D018840:HSP70 Heat-Shock Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D005947:Glucose