Table 1.
Recent major studies on experimental blast injury with different parameters assessed (behavioral, neuropathological, and biomarker changes).
| Reference | Animal model/device used-BOP intensity | Time point assessment post injury | Repeats of blast and time between exposure | Additional variables studied | Behavioral assessment (if available) | Neuro, systemic, and other organ-specific pathology/biomarkers parameters |
|---|---|---|---|---|---|---|
| Abdul-Muneer et al. (102) | Rat/primary blast/shock tube/123 kPa | 1/6/6/24/48 h/8 days | One or two (24 h between intervals) | None | Vascular damage, BBB leakage, neuroinflammation MMPs changes, AQP-4, oxidative stress (4HNE-3-NT), and edema; S100B and NSE (serum) | |
| Ahmed et al. (136) | Rat/compressed air-driven shock tube/138 kPa | 1, 3, 7, 14, 26, 36, and 42 days | Single or five (24 h between each blast) | Repeated vs. single blast comparison | Oxidative stress, vascular abnormalities, neuronal, and glial cell death | |
| Arun et al. (137) | Mouse/A compressed air-driven shock tube/21 psi | 6 or 24 h | Three blast (1.5 min) | Mice restrained in the prone position with a tautly-drawn net | Initial decrease and later increase GFAP and total tau proteins (liver, spleen, brain, and plasma) | |
| Zou et al. (138) | Rat/5 kg TNT and PETN detonation: 3 m distance (high exposure, 480 kPa) and 2 m distance (low injury, 180 kPa) | 24, 72 h and 2 weeks | Single | None | Retina injury: blast-dependent increase in VEGF, iNOS, eNOS, nNOS, AQP4, GFAP, elevated inflm cytokines, and chemokines | |
| Prima et al. (139) | Rat/composite blast with head acceleration and Primary blast with no acceleration/230–380 kPa | 6 h and 1 and 7 days | Single | Primary blast vs. composite’ blast animals are body armored | Thrombin generation (TG) serum integrin α/β, sE-selectin, sICAM-1, and matrix metalloproteinases MMP-2, MMP-8, and MMP-13 | |
| Tumer et al. (104) | Rat/compressed air-driven shock tube ~2 m distance/358 kPa for 10 ms/noise level noise level (100–105 dB) | 6 h | Single | None | Increased oxidative stress; activation of the sympatho-adrenal medullary axis; (TH), dopamine-β hydroxylase (DβH), neuropeptide Y (NPY) plasma norepinephrine (NE); diffused neuronal injury | |
| Genovese et al. (135) | SD-rat/shock tube airblast exposure 74.5 kPa | Every 7 days for 8 weeks | 1/day for 3 days | None | Conditioned fear/PTSD | Neuronal pathology |
| Huber et al. (131) | Mouse/compressed gas-driven shock tube | 24 and 30 days | Single | None | Elevation of multiple phospho-, cleaved-tau, and (MnSOD or SOD2) levels | |
| Sajja et al. (140) | Rat/helium shock tube/117 kPa | 7.5 ms | 24, 48 h | Magic angle spinning 1H MRS analysis | Elevated N-acetyl aspartate, glutamate, and increased GFAP, Bcl-2, Bax, caspase-3, signs excitotoxicity (glutamate/creatine; hippocampal neuronal loss; mitochondrial distress | |
| Skotak et al. (141) | Rat/helium driven shock tube/(130, 190, 230, 250, and 290 kPa) | 24 h | Single | Biomechanical loading assessed with pressure gauges (thorax, cranial space, and nose) | Diffuse blood-brain barrier breakdown in brain parenchyma; fatality; lung hemorrhage; no evident neuronal injury | |
| Valiyaveettil et al. (34) | Mouse/blast overpressure/20.6 psi | 4, 24, and 72 h | Three times (1–30 min) | None | Platelet serotonin decreased at 4 h post blast; increase in the plasma serotonin levels. Increase in blood, plasma, and brain myeloperoxidase enzyme activity. Constriction of blood vessels of the brain | |
| Takeuchi et al. (142) | Rats/laser-induced shock waves/0.5–1, 0.5 J/cm2 | 14 days | Single | None | Decrease in the CB (cingulum bundle) axonal density | |
| Turner et al. (143) | Rats/tabletop shock tube/31, 50, 72, and 90 psi | 72 h | Single | Thorax and abdomen protection | Neural degeneration; increased glial activation (GFAP); extensive intracranial bleeding leading to death | |
| Tweedie et al. (144) | Mouse/concussive head trauma (weight drop with metal protection)/explosion shock wave pressure (7 m distance ~2.5 psi–17.2 kPa) | 7 days | Single | Comparison between mild TBI and blast injury | Altered cognitive and emotional behaviors (Y maze, novel object recognition passive avoidance/elevated plus maze cognition and anxiety | Altered hippocampal gene expression |
| Cho et al. (134) | Mouse/bast chamber (compression wave attached to a PVC tube)/94, 123, and 181 kPa | 7, 14, 28 days and 3 months | Single | Body is protected with fiberglass screen mesh/hearing loss model | Decreased spiral ganglion neurons (SGNs) and afferent nerve synapses, loss of outer hair cells (OHCs), tinnitus, hearing loss | |
| Yeoh et al. (103) | SD rat, rifle primary shock tube (145, 232, and 323 kPa) | 5 min and 24, 48 h | Single | None | IgG assessment cardiovascular injury due to primary blast injury is distinct from a typical TBI | |
| Cho et al. (134) | Male SD rat, shock tube 129.23 ± 3.01 kPa for 2.5 ms | 4, 24, 48 h and 2 weeks post BOP | Single | None | Short term memory | Immunological assessment (TMF-γ, MCP-1) neuronal loss |
| Ahlers et al. (145) | Rat/pneumatically driven shock tube at 116.7, 74.5, and 36.6 kPa | 6, 24 h and 1 week | Single or 12 blasts (24 h at 36.6 kPa) | Three body orientation (sideway, facing away vs. frontal) | Morris water maze task 116.7 kPa demonstrated transient alteration or loss of consciousness, 74.5 kPa demonstrated anterograde memory deficits | Subdural hemorrhage and cortical contusions |
| Ahmed et al. (146) | Swine/blast overpressure/mild (24–37 psi) or moderate (40–52 psi) | 6, 24, 72 h and 2 weeks | Single | None | CSF biomarkers (CK-BB NFH, GFAP, S100B, VEGF, Claudin 5, and NSE); neuronal and glial cell damage, altered vascular permeability, and inflammation | |
| Balakathiresan et al. (123) | Rat/air-driven shock tube 120 kPa | 3 and 24 h | Short interval (three times – 2 h), long interval (three times – 24 h each) | None | CSF and serum miRNAs (let-7i) | |
| Hines-Beard et al. (147) | Mouse/primary ocular blast injury; pressurized air tank with paintball gun/23.6, 26.4, and 30.4 psi) | 3,7, 14, and 28 days | Visual acuity deficit detected in 30 psi group eyes via optokinetics | Retinal damage was present in the eyes from the 30 psi group-corneal edema, corneal abrasions, at optic nerve avulsion | ||
| Bir et al. (148) | Rat/gas-driven shock tube, 90, 103, 117, 193, and 159 kPa | 24, 48, and 72 h | Single | None | MRI analysis showed hippocampal reduction in the Cerebral Blood Flow | |
| Kovesdi et al. (150) | Rat/shock tube/20.6 psi | 8 and 45 days | Single | Minocycline (50 mg/kg i.p. NSAID); mitigate neurobehavioral changes/body protection | Impaired memory and increased anxiety. (open field, elevated plus maze, and Barnes maze) minocycline showed neuroprotection | Elevated brain and Serum: CRP, MCP-1, NFH, NSE, Tau, GFAP, MBP, S100B, CRP, MCP-1, TLR-9, Claudin 5, and AQP4 |
| Li et al. (95) | Macaca fascicularis/120 kg of TNT/80 and 200 kPa | 3 days and 1 month | Single and double (3 days interval at 80 kPa) | Monkey Cambridge neuropsychological test automated battery motor coordination and working memory | Increased (AQP-4) white matter degeneration, astrocyte hypertrophy; MRI revealed ultrastructural in Purkinje neurons in the cerebellum and hippocampal pyramidal neurons | |
| Rafaels et al. (51) | Ferrets/8′shock tube/variable peak overpressure (98–818 kPa range) | 1–5 h | Direct recording | Head exposure/thorax and abdomen protection | Apnea; brain bleeding; fatality | |
| Shridharani et al. (153) | Pigs/compressed-gas shock tube/variable (107–740 kPa range) | 1.3–6.9 ms | Direct recording | Heads exposed/lungs and thorax protected (ballistic protective vests) | Apnea intracranial pressures indicates pressure attenuation by the skull up to a factor of 8.4 | |
| Sundaramurthy et al. (96) | Rat/Nebraska’s shock tube/100, 150, 200, and 225 kPa) | NA | Single | Variable Animal Placement Location along the shock tube (i.e., inside, outside, and near the exit) | Surface and intracranial pressure elevation linearly with the incident peak overpressures | |
| Svetlov et al. (92) | Rat, external shock tube (230–380 kPa) | 1 and 7 days post trauma | Single | Primary and composite blast | Persistent gliosis accumulation of GFAP/CNPase in circulation as well as IL-1/IL-10 fractalkine, orexin A, VEGF-R, NRP-2 increased after primary, and composite; integrin-α/β, ICAM-1, L-selectin, NGF-β increased after primary blast | |
| Elder et al. (154) | Rat/air blast shock tube (WRAIR)/74.5 | 4.5 months | Three times (24 h) | Anxiety and fear; locomotor activity, MWM, rotarod, elevated zero arm, predator scent exposure; movement restricted with shielding; contextual and cued fear conditioning | Elevation in the amygdala of the protein stathmin 1 (proteomic changes) | |
| Dalle Lucca et al. (155) | Rat/compressed air-driven shock tube/120 kPa | 0.5, 3, 48, 72, 120, and 168 h | Two | None | Hemorrhage and edema in the brain cortex; elevated TNF-α, C3/C5b-9, and AQP-4; increased leukocyte infiltration | |
| Arun et al. (22) | In-vitro 96 well plates-SH-SY5Y human neuroblastoma cells bTBI model/compressed air-driven shock tube (13.68, 18.03, and 21.05 psi) | 24 h | Sing1e or three times (2 min intervals at 21.05 psi) | Plate orientation (horizontal vs. vertical) | Decreased ATP levels, increased LDH, and ROS; downregulation of CyPA protein | |
| Chavko et al. (62) | Rat/air-driven shock tube/36 kPa point-pressure measurements of cerebral ventricles | ~2.94 ms | Single | Head orientation (head facing blast, right side exposed, head facing away) | Pressure wave propagation and head orientation dependence | |
| Kuehn et al. (156) | Rat/cranium only blast injury apparatus/137.9–515 kPa | 24 h and 7 and 10 days | Single | None | Accelerating rotarod; apnea | H&E staining subarachnoid hemorrhages; brain injury (caspase-3, and β-amyloid precursor protein (β-APP), IgG labeling, and Fluoro-Jade C); cardiac arrest; vasogenic edema |
| Cernak et al. (157) | Mouse/helium modular, multi-chamber shock tube/mild (183 kPa) moderate (213 kPa), severe (295 kPa) | 1–5, 7, 10, 14, 21, and 30 days | Single | Supine vs. prone position) | Motor, cognitive, and behavioral) outcomes, assessed via : rotarod, anxiety learning, and memory via active avoidance procedure | Inflammation elevated in tissue CCL, osteopontin, MRP8, ED1, and GFAP at different time points |
| Koliatsos et al. (50) | Mouse/helium multi chamber shock tube/high (25–45 psi), low (2.1 psi) | 3, 5 days (biochem testing) and 7–14 (behavioral) | Single | Either Head or Torso Covered | Rotarod, Y maze open field social and spatial recognition memory and motor deficits | Axonal swellings (injury), APP, but degeneration staining 7–14 days after exposure |
| Kovesdi et al. (149) | Rat/compression-driven shock tube/20.6 psi | 15, 44, 66 days (behavioral) and 66 days (biochemical) | Single | Enriched environment (EEN) contribution | Memory problems, increased anxiety, and depression; improved spatial memory in EEN | Axonal degeneration; elevation in IL-6, IFNγ VEGF, and tau protein levels; hippocampal GFAP and DCX |
| de Lanerolle et al. (53) | Swine/explosive blast levels in three scenarios: simulated free field (35 psi), high-mobility, vehicle (65 psi), and building setup (63 psi) | 72 h and 2 weeks | Single | Blast varied settings: blast tube, high mobility; multipurpose wheeled vehicle, and four-sided structure | Little neuronal injury, fiber tract demyelination, or intracranial hemorrhage observed; increased astrocyte activation; bulbs positive for BAPP | |
| Pun et al. (47) | Rat/120 kg of 2,4,6-trinitrotoluene (TNT)/48.9 kPa (7.1 psi) or 77.3 kPa (11.3 psi) at 24 or 40 m | 1, 4, and 7 days | Single | Concrete block was placed between the animals and the explosive source at a distance of 1.5 m from the animals | Cortical neurons were “darkened” and shrunken with narrowed vasculature (day 1, not at 4–7 days); no Iba-1 change; TUNEL-positive cells in the white matter of the brain (day 1); an increase in APP in the white (acute axonal damage); genomics analysis showed signs of repair at day 4 and 7 post-blast | |
| Reneer et al. (151) | Rat/multi-mode shock tube, the McMillan blast device (compressed air/helium driven tube mode, or oxyhydrogen – RDX explosives mode/ 100, 150, and 200 kPa) | 3 min post blast | Single | Two overpressure modes (air vs. explosives), Kevlar vest body protection | Rats exposed to compressed air-driven blasts had more pronounced vascular damage than those exposed to oxyhydrogen-driven blasts of the same peak overpressure | |
| Risling et al. (152) | Rat/blast tube with pressure wave/130 and 260 kPa | 2 h, 1, 3, 5 days, and 3 weeks | Three groups comparison – (1) fixed no head acceleration forces; (2) controlled penetration of a 2-mm thick needle; and (3) high-speed sagittal rotation angular acceleration | Diffuse axonal injury (DAI) in penetration and rotation models; genomics changes in the expression in a large number of gene families cell death, inflammation, and neurotransmitters in the hippocampus (acceleration and penetration injuries); downregulation of genes involved in neurogenesis and synaptic transmission | ||
| Rubovitch et al. (93) | Mouse/open field explosives ~500 g TNT detonation (1 m elevated)/5.5 and 2.5 psi | 30 days | Mice in plastic net 4 or 7 m; MRI and DTI analysis | Significant decrease in cognitive and behavioral (Y maze; hippocampal function and spatial memory; novel object recognition task | Increased BBB permeability; 1 month post-blast; increase in fractional anisotropy (FA); no visible organ damage; and elevated MnSOD2 | |
| Connell et al. (158) | Female Guinea pig/2.5-cm strips of shock tubing/(23, 41, and 64 kPa | 30 min | Ex vivo model of spinal cord white; shock tubing (explosive lining of 0.1 grain/foot composed of tetranitramine and aluminum) | Nervous tissue compression, and increased axonal permeability | ||
| Garman et al. (54) | Rat/helium-driven shock tube/35 psi (4 ms) | 24, 72 h and 2 week | Head exposure with body armor | Increased blood–brain barrier permeability; elevated APP, GFAP, Iba1, ED1, and rat IgG. | ||
| Gyorgy et al. (122) | Pig/compression-driven shock tube/~20, 20–40, and ~40 psi | 6, 24, 72 h and 2 week | None | Serum elevation of S100B, MBP, and NF-H, but not NSE | ||
| Readnower et al. (44) | Rat/air-driven shock tube/120 kPa | 3, 24 h and 5 days | Single | None | BBB breakdown: At 3 and 24 h post exposure; increase in IgG staining in the cortex; brain oxidative stress: (4-HNE) and (3-NT) were significantly increased at 3 h post exposure and returned to control levels at 24 h post exposure; and microglia activation: at 5 days | |
| Cheng et al. (159) | Rat/electric detonator with the explosive equivalent of 400 mg TNT (100, −400 kPa) (distance of 5, 7.5, and 10 cm) | 1, 2, 3, 5, and 7 days | Single | Head orientation(frontal, parietal, and occipital head exposure) | 87% Rats developed apnea, limb seizure, poor appetite, and limpness | Diffuse subarachnoid hemorrhage and edema; cortical capillary damage; and tissue water and NSE |
| Cai et al. (160) | Rat/5 g compressed dynamite stick (75 cm from chest) | 3, 6, 12 h and 1, 2, 3, 7 days | Single | Blast vs. burn-blast | Serum neutrophil elastase (NE); water lung content | |
| Long et al. (10) | Rat/compression-driven shock tube/126 and 147 kPa | 24 h | Single | Kevlar – protective vest (thorax – abdomen) | MWM testing beam walking and spatial navigation(disrupted neurologic neurobehavioral performance) | Heart rate, MAP, brain axonopathy, and widespread fiber degeneration |
| Säljö et al. (42) | Rat shock tube/10, 30, and 60 kPa (4 ms) | 0.5, 3, 6, and 10 h and 1, 2, 3, 5, and 7 days | Single | Morris water maze: impaired cognitive function: 48 h post injury | Dose-dependent rise in intracranial pressure ICP in rats exposed to blast and an increasing time delay in elevation with decreasing intensity of exposure. the ICP returned to control levels after 7 days | |
| Säljö et al. (41) | Pig – Howitzer (9 and 30 kPa); Bazooka (42 kPa); automatic rifle (23 kPa) | 3 and 7 days | Three (exposure in air; 15 min intervals) two (exposure under water; 6–7 min) | Comparison of pressure time of different blast overpressure in: air, underwater, and localized blast | In pig study: small parenchymal and subarachnoid hemorrhages, predominately in the occipital lobe, cerebellum, and medulla oblongata; no observation in rat study | |
| Rat/shock tube (8.7 kPa) | ||||||
| Cernak et al. (45) | Rat/large-scale BT-I shock tube/3389 kPa and small-scale BT-III shock tube (440 kPa) | 3, 24 h and 5 days | Single | Protected head vs. whole body exposure | Deficits in active avoidance task | Swellings of neurons, glial reaction, and myelin debris in the hippocampus, laminal body and vacuoles formation (electron microscope) |
B APP, B-amyloid precursor protein; GFAP, glial fibrillary acidic protein; AQP-4, aquaporin-4; MnSOD or SOD2, manganese superoxide-dismutase l; UCH-L1, ubiquitin C-terminal hydrolase; vWF, von Willebrand factor; NA, not applicable; NSE, neuronspecific enolase; Mwm, Morris water maze; CK-BB, brain-specific creatine kinase; MAP, mean arterial pressure; H&E, hematoxylin and eosin; 4-HNE, 4-hydroxynonenal; 3-NT, 3-nitrotyrosine; TNT, 2,4,6-trinitrotoluene; RDX, oxyhydrogen; ms, milliseconds; MMP8, matrix metalloproteinase 8; BOP, blast over pressure; NF-H, neurofilament-heavy chain.