Morphologic and biochemical characterization of brain injury in a model of controlled blast overpressure exposure.
OBJECTIVE
Existing experimental approaches for studies of blast impact in small animals are insufficient and lacking consistency. Here, we present a comprehensive model, with repeatable blast signatures of controlled duration, peak pressure, and transmitted impulse, accurately reproducing blast impact in laboratory animals.


METHODS
Rat survival, brain pathomorphology, and levels of putative biomarkers of brain injury glial fibrillary acid protein (GFAP), neuron-specific enolase, and ubiquitin C-terminal hydrolase (UCH)-L1 were examined in brain, cerebrospinal fluid (CSF), and blood after 10 msec of 358 kPa peak overpressure blast exposure.


RESULTS
The high-speed imaging demonstrated a strong head acceleration/jolting accompanied by typical intracranial hematomas and brain swelling. Microscopic injury was revealed by prominent silver staining in deep brain areas, including the nucleus subthalamicus zone, suggesting both diffused and focal neurodegeneration. GFAP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), markers of astroglia and oligodendroglia, accumulated substantially in the hippocampus 24 hours after blast and persisted for 30 days postblast. However, GFAP content in the blood significantly increased 24 hours after injury, followed by a decline and subsequent accumulation in CSF in a time-dependent fashion. A similar profile is shown for UCH-L1 increase in blood, whereas increased CSF levels of UCH-L1 persisted throughout 14 days after blast and varied significantly in individual rats. Neuron-specific enolase levels in blood were significantly elevated within 24 hours and 48 hours postblast.


CONCLUSIONS
The proposed model of controlled nonpenetrating blast in rats demonstrates the critical pathologic and biochemical signatures of blast brain injury that may be triggered by cerebrovascular responses, including blood-brain barrier disruption, glia responses, and neuroglial alterations.
Svetlov
Stanislav I
SI
Center of Innovative Research, Banyan Biomarkers, Inc, Alachua, Florida 32615, USA. ssvetlov@banyanbio.com
Prima
Victor
V
Kirk
Daniel R
DR
Gutierrez
Hector
H
Curley
Kenneth C
KC
Hayes
Ronald L
RL
Wang
Kevin K W
KK
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000399:Air Pressure; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001753:Blast Injuries / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000502:physiology; D015153:Blotting, Western; D001924:Brain Concussion / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology; D020833:Diffuse Axonal Injury / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000293:injuries / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D009418:S100 Proteins / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009418:S100 Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D010751:Phosphopyruvate Hydratase