title: Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats.
abstract: BACKGROUND
  Blast-induced neurotrauma (BINT) is the signature life threatening injury of current military casualties. Neuroinflammation is a key pathological occurrence of secondary injury contributing to brain damage after blast injury. We have recently demonstrated that blast-triggered complement activation and cytokine release are associated with BINT. Here, we evaluated if administration of the complement inhibitor recombinant human decay-accelerating factor (rhDAF) is beneficial on neuroinflammation and neurodegeneration in a rat model of moderate BINT. Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood-brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.
  
  
  RESULTS
  Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood-brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP.
  
  
  CONCLUSIONS
  These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.
authors.affiliation: Immunomodulation of Trauma Program, US Army Institute of Surgical Research, 3650 Chambers Pass, BHT2/Building 3610, Fort Sam Houston, TX 78234, USA. Jurandir.dallelucca@us.army.mil.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Li
authors.forename: Mikulas
authors.initials: M
authors.lastname: Chavko
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Slack
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Richard M
authors.initials: RM
authors.lastname: McCarron
authors.forename: James D
authors.initials: JD
authors.lastname: Ross
authors.forename: Jurandir J
authors.initials: JJ
authors.lastname: Dalle Lucca
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000150:complications*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D018958:CD55 Antigens / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology; D015213:Neuroimmunomodulation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011312:Pressure; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018958:CD55 Antigens; D016207:Cytokines; D018696:Neuroprotective Agents