title: Rodent model of direct cranial blast injury.
abstract: Traumatic brain injury resulting from an explosive blast is one of the most serious wounds suffered by warfighters, yet the effects of explosive blast overpressure directly impacting the head are poorly understood. We developed a rodent model of direct cranial blast injury (dcBI), in which a blast overpressure could be delivered exclusively to the head, precluding indirect brain injury via thoracic transmission of the blast wave. We constructed and validated a Cranium Only Blast Injury Apparatus (COBIA) to deliver blast overpressures generated by detonating .22 caliber cartridges of smokeless powder. Blast waveforms generated by COBIA replicated those recorded within armored vehicles penetrated by munitions. Lethal dcBI (LD(50) ∼ 515 kPa) was associated with: (1) apparent brainstem failure, characterized by immediate opisthotonus and apnea leading to cardiac arrest that could not be overcome by cardiopulmonary resuscitation; (2) widespread subarachnoid hemorrhages without cortical contusions or intracerebral or intraventricular hemorrhages; and (3) no pulmonary abnormalities. Sub-lethal dcBI was associated with: (1) apnea lasting up to 15 sec, with transient abnormalities in oxygen saturation; (2) very few delayed deaths; (3) subarachnoid hemorrhages, especially in the path of the blast wave; (4) abnormal immunolabeling for IgG, cleaved caspase-3, and β-amyloid precursor protein (β-APP), and staining for Fluoro-Jade C, all in deep brain regions away from the subarachnoid hemorrhages, but in the path of the blast wave; and (5) abnormalities on the accelerating Rotarod that persisted for the 1 week period of observation. We conclude that exposure of the head alone to severe explosive blast predisposes to significant neurological dysfunction.
authors.affiliation: Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA.
authors.forename: Reed
authors.initials: R
authors.lastname: Kuehn
authors.forename: Philippe F
authors.initials: PF
authors.lastname: Simard
authors.forename: Ian
authors.initials: I
authors.lastname: Driscoll
authors.forename: Kaspar
authors.initials: K
authors.lastname: Keledjian
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ivanova
authors.forename: Cigdem
authors.initials: C
authors.lastname: Tosun
authors.forename: Alicia
authors.initials: A
authors.lastname: Williams
authors.forename: Grant
authors.initials: G
authors.lastname: Bochicchio
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology; D000465:Algorithms; D000818:Animals; D001369:Axons / Q000473:pathology; D001753:Blast Injuries / Q000473:pathology*; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology*; D004195:Disease Models, Animal; D004867:Equipment Design; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000473:pathology; D010092:Oximetry; D004856:Postural Balance / Q000502:physiology; D011312:Pressure; D051381:Rats; D020318:Rats, Long-Evans; D015203:Reproducibility of Results; D013345:Subarachnoid Hemorrhage / Q000473:pathology; D014724:Vestibular Function Tests; D014722:Vestibule, Labyrinth / Q000503:physiopathology