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.

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

“…19,20,[22][23][24][25][26]28,[30][31][32][33][128][129][130][131][132][133] These approaches avoid the severe focal contusive brain injury associated with open-skull TBI models, while a single exposure, depending on the blast pressure, can yield axonal injury, microglial activation, edema, and cognitive, emotional, and visual deficits, 20,23,24,26,28,30,31,33,[128][129][130][131]133,134 similar to those observed with our focal blast model. For example, significant rotarod motor deficits and axonal swellings have been reported for 2 weeks after a whole body 15-psi blast in mice, 19,24 and hippocampal neuron loss has been reported in rats 2 weeks after whole body 18-psi blast.…”

“…This range includes pressures that were previously reported to produce TBI in rats and mice exposed to head or whole body blasts. 20,21,[24][25][26]30,33 We also measured the pressure detected by the pressure gauge at increasing distances of the tip of the pressure gauge barrel from the gun barrel tip, at a series of blast gun input tank pressure settings, and determined that the blast gun output pressure was uniform over a distance of 3-5 mm from the tip of the blast gun. Accordingly, we measured the pressure waves produced at different peak output blast settings at 4-5-mm from the blast gun tip, and mice were also subsequently positioned at this distance.…”

“…8,[10][11][12][13][14][15][16][17][18] Some researchers have used shock tubes to deliver compressed air blasts to the animal, to mimic blast-produced TBI. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] These models, however, are often accompanied by hypoxia and blood pressure surges resulting from compression of the lungs, heart, and aorta, which in turn damage brain blood vessels. 8,34 Moreover, the direct exposure of the eye to the blast makes it difficult to distinguish visual deficits caused by brain trauma from visual deficits caused by the direct ocular impact of the blast.…”

Glyburide-Novel Prophylaxis and Effective Treatment for Traumatic Brain Injury

“…1 Our published data demonstrate our central thesis, that exposure of the head alone to severe blast predisposes to significant neurological dysfunction.…”

“…The specific objectives of this research project may be summarized as follows: (1) develop a standardized rat model of blast-TBI, to permit study of direct transcranial effects of blast on the brain, independent of indirect transthoracic blast effects; (2) using this rat model, determine the specific role of the SUR1-regulated NCCa-ATP channel in blast-TBI, including testing whether block of SUR1 using glibenclamide would show a beneficial effect in blast-TBI; (3) in normal human volunteers, determine the safety of oral glibenclamide as it might be used as prophylaxis against blast-TBI.…”