Rodent model of direct cranial blast injury

Reed Kuehn, Philippe F. Simard, Ian Driscoll, Kaspar Keledjian, Svetlana Ivanova, Cigdem Tosun, Alicia Williams, Grant Bochicchio, Volodymyr Gerzanich, J. Marc Simard

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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 ∼ 515kPa) 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 15sec, 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.

Original languageEnglish (US)
Pages (from-to)2155-2169
Number of pages15
JournalJournal of Neurotrauma
Volume28
Issue number10
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

Keywords

  • β-amyloid precursor protein caspase-3
  • primary blast injury
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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