title: Blast-induced moderate neurotrauma (BINT) elicits early complement activation and tumor necrosis factor α (TNFα) release in a rat brain.
abstract: Blast-induced neurotrauma (BINT) is a major medical concern yet its etiology is largely undefined. Complement activation may play a role in the development of secondary injury following traumatic brain injury; however, its role in BINT is still undefined. The present study was designed to characterize the complement system and adaptive immune-inflammatory responses in a rat model of moderate BINT. Anesthetized rats were exposed to a moderate blast (120 kPa) using an air-driven shock tube. Brain tissue injury, systemic and local complement, cerebral edema, inflammatory cell infiltration, and pro-inflammatory cytokine production were measured at 0.5, 3, 48, 72, 120, and 168 h. Injury to brain tissue was evaluated by histological evaluation. Systemic complement was measured via ELSIA. The remaining measurements were determined by immunohistoflourescent staining. Moderate blast triggers moderate brain injuries, elevated levels of local brain C3/C5b-9 and systemic C5b-9, increased leukocyte infiltration, unregulated tumor necrosis factor alpha (TNFα), and aquaporin-4 in rat brain cortex at 3- and 48-hour post blast. Early immune-inflammatory response to BINT involves complement and TNFα, which correlates with hippocampus and cerebral cortex damage. Complement and TNFα activation may be a novel therapeutic target for reducing the damaging effects of BINT inflammation.
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: Jurandir J
authors.initials: JJ
authors.lastname: Dalle Lucca
authors.forename: Mikulas
authors.initials: M
authors.lastname: Chavko
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
authors.forename: Saleena
authors.initials: S
authors.lastname: Adeeb
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Falabella
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Slack
authors.forename: Richard
authors.initials: R
authors.lastname: McCarron
authors.forename: Yansong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D003167:Complement Activation / Q000276:immunology*; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha