Table 2.
Effects of low-level blast exposure in animal models.
| Species | Peak overpressure (shock tube unless otherwise indicated); duration and impulse given when reported | Pathological, biochemical, physiological, and imaging findings | Behavioral findings | Reference |
|---|---|---|---|---|
| Rat | 2.8 or 20 kPa (duration ≈2 ms) | 20 kPa exposure resulted in decreased performance on rotametric and grip-strength tests; scattered hyperchromatic cells visible in the cerebral cortex at 1 day or 1 week post-exposure; animals receiving aminoguanidine before or after blast protected. | (134) | |
| Rat | 40 kPa (duration 4 ms) | Sensor in third ventricle detected blast pressure wave in brain with similar magnitude to that in air. | (131) | |
| Rat | 10, 30, or 60 kPa (duration 4–6 ms) | Intracranial pressure (ICP) increases of 80–145% at 10 h post-blast at 30 and 60 kPa exposures; ICP increases less in rats fed processed cereal feed. | Morris water maze (MWZ) impaired 2 days after exposure to 10 or 30 kPa blast; no functional impairment on MWZ in rats fed processed cereal feed. | (119) |
| Rat | Open-field exposure (120 kg TNT) 48.9 kPa (7.1 psi; duration 14.5 ms) or 77.3 kPa (11.3 psi; duration 18.2 ms) | Cortical neurons darkened and shrunken with narrowed vasculature in cerebral cortex 1 day after blast; TUNEL-positive oligodendrocytes and astrocytes in white matter at day 1; more amyloid precursor protein immunoreactive cells in white matter; altered expression of over 5700 genes in the brain post-blast. | (118) | |
| Rat | 35 kPa (duration 4.1 ms) | Pressure wave transmitted to brain; frontal exposures (head facing blast) resulted in pressure traces of higher amplitude and longer duration than side exposure or head facing away from blast. | (130) | |
| Mouse | Open-field explosives; 4 and 7 m distance from blast (5.5 and 2.5 psi) | Increased blood–brain barrier permeability 1 month post-blast on MRI T1 weighted images; increase in fractional anisotropy (FA) and decrease in radial diffusivity on diffusion tensor imaging (DTI); upregulation of manganese superoxide dismutase 2 in neurons and CXC-motif chemokine receptor 3 around blood vessels in fiber tracts. | Reduced preference for a novel object at 7 and 30 days post-blast; more rearing events in a staircase climbing task at 7 and 30 days post-blast; less alteration in a Y-maze task at 7 days (2.5 and 5.5 psi exposures) and 30 days (5.5 psi exposure) after blast exposure. | (127) |
| Rat | 11.5 kPa (duration 200–250 μs) | Delayed cytoskeletal proteolysis of alpha II-spectrin in cortex and hippocampus by 12 h post-injury; cell death minimal and localized predominantly in corpus callosum and periventricular regions; evoked compound action potentials (CAP) in the corpus callosum increased in duration at 14 and 30 days post-injury with depression of unmyelinated fiber amplitudes; shielding head attenuated alpha II-spectrin cytoskeletal breakdown. | (117) | |
| Rat | Single 36.6 kPa (duration of 4.1 ms, impulse 75.2 kPa*ms) and 74.5 kPa (duration 4.8 ms, impulse 175.8 kPa*ms); repeat (12) 36.6 kPa | No general histopathology; no evidence of axonal pathology based on APP immunohistochemical staining. | Anterograde memory deficits on a passive avoidance task after 74.5 kPa exposure; repeat exposure to 36.6 kPa produced transitory learning deficits on MWZ. | (107) |
| Rat | Repeat (three) 74.5 kPa (duration 4.8 ms, impulse 175.8 kPa*ms) | Elevation in the amygdala of the protein stathmin 1. | Increased anxiety, enhanced acoustic startle, and enhanced response in the contextual phase of a fear-conditioning paradigm in blast exposed; altered response to a predator scent after blast exposure. | (109) |
| Rat | Single 36.6 or 74.5 kPa (duration 4.8 ms, impulse 175.8 kPa*ms) | Brain Aβ levels decreased acutely following exposure; levels of APP protein increased on Western blotting although no evidence of axonal pathology based on APP immunohistochemical staining; no change in levels of β-site APP cleaving enzyme 1 (BACE1), or the γ-secretase component presenilin-1. | (135) | |
| Rat | Single or multiple (three) 74.5 kPa (duration 4.8 ms, impulse 175.8 kPa*ms) | No general histopathology but focal cortical lesions thought to represent shear-related lesions found in many brains. | (110) | |
| Mouse | Single live explosive detonations (2.5–5.5 psi peak overpressure). | Increased ganglioside GM2 in hippocampus, thalamus, and hypothalamus with depletion of ceramides. | (129) | |
| Mouse | 2.5 psi (17.2 kPa) | Compared hippocampal transcriptome in mice subjected to weight drop or blast injury; divergence in hippocampal transcriptome observed between models; Alzheimer’s disease-related pathways displayed a markedly different form of regulation depending on the type of TBI. | Reduced preference for a novel object at 7 and 30 days post-blast; no changes in Y-maze, passive avoidance, or elevated plus maze. | (128) |
| Rat | 74 kPa (duration ≈4 ms) | Two weeks after exposure, little or no changes in a panel of common injury markers in cortex, corpus callosum, or hippocampus; no change in spectrin breakdown products in brain; significant shortening of the axon initial segment (AIS) in cortex and hippocampus of blast-exposed; next highest pressure (98 kPa) resulted in lung trauma and death. | Rats exposed to a blast spent less time exploring a novel object at 2 weeks post-exposure. | (121) |
| Rat | 100 kPa (duration 0.46 ms) | Region specific decreases in fractional anisotropy on DTI in blast-exposed animals at 4 and 30 days post-exposure; evolution of DTI changes during the 4–30-day post-blast period with greater changes at 30 days. | Deficits in memory in MWZ and less activity in an open field at 4 and 30 days; no changes blast vs. control in an elevated plus maze. | (116) |
| Mouse | 100 db noise exposure coupled with a 2 psi (duration 0.5 ms) air blast administered in sessions of 60 exposures over 1 min. | Impaired object recognition and evidence of anxiety in an elevated O-maze; following noise/blast exposure mice spent less time at the edges of an open-field chamber. | (108) | |
| Rat | Repeat (three) 74.5 kPa (duration 4.8 ms, impulse 175.8 kPa*ms) | Blast exposure caused more rapid extinction of a conditioned fear response if the overpressure injury was administered after learning of the conditioned fear response. | (136) | |
| Mice | 20–60 psi blast exposures delivered to a focal area on one side of the cranium. | 25–40 psi blast exposures produced transient anxiety in an open field; mice exposed to 50–60 psi blast exposures exhibited increased acoustic startle, perseverance of a learned fear response, an enhanced contextual fear response, depression-like behavior, and diminished prepulse inhibition. | (126) | |
| Rat | Single or multiple (three) 74.5 kPa (duration 4.8 ms, impulse 175.8 kPa*ms) | Microvascular pathology present at 24 h after injury within an otherwise normal neuropil; chronic changes in the microvasculature evident many months after blast exposure. | (111) |