title: Exposure of the thorax to a sublethal blast wave causes a hydrodynamic pulse that leads to perivenular inflammation in the brain.
abstract: Traumatic brain injury (TBI) caused by an explosive blast (blast-TBI) is postulated to result, in part, from transvascular transmission to the brain of a hydrodynamic pulse (a.k.a., volumetric blood surge, ballistic pressure wave, hydrostatic shock, or hydraulic shock) induced in major intrathoracic blood vessels. This mechanism of blast-TBI has not been demonstrated directly. We tested the hypothesis that a blast wave impacting the thorax would induce a hydrodynamic pulse that would cause pathological changes in the brain. We constructed a Thorax-Only Blast Injury Apparatus (TOBIA) and a Jugular-Only Blast Injury Apparatus (JOBIA). TOBIA delivered a collimated blast wave to the right lateral thorax of a rat, precluding direct impact on the cranium. JOBIA delivered a blast wave to the fluid-filled port of an extracorporeal intravenous infusion device whose catheter was inserted retrograde into the jugular vein, precluding lung injury. Long Evans rats were subjected to sublethal injury by TOBIA or JOBIA. Blast injury induced by TOBIA was characterized by apnea and diffuse bilateral hemorrhagic injury to the lungs associated with a transient reduction in pulse oximetry signals. Immunolabeling 24 h after injury by TOBIA showed up-regulation of tumor necrosis factor alpha, ED-1, sulfonylurea receptor 1 (Sur1), and glial fibrillary acidic protein in veins or perivenular tissues and microvessels throughout the brain. The perivenular inflammatory effects induced by TOBIA were prevented by ligating the jugular vein and were reproduced using JOBIA. We conclude that blast injury to the thorax leads to perivenular inflammation, Sur1 up-regulation, and reactive astrocytosis resulting from the induction of a hydrodynamic pulse in the vasculature.
authors.affiliation: 1 Department of Neurosurgery, University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.forename: Adam
authors.initials: A
authors.lastname: Pampori
authors.forename: Kaspar
authors.initials: K
authors.lastname: Keledjian
authors.forename: Cigdem
authors.initials: C
authors.lastname: Tosun
authors.forename: Gary
authors.initials: G
authors.lastname: Schwartzbauer
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ivanova
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology*; D004195:Disease Models, Animal; D057446:Hydrodynamics; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D013909:Thorax
keywords: ED-1; GFAP; Sur1, TNF-α; blast-TBI; perivenular inflammation