Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model.
Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0-450 kPa (0-800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146-220 kPa and 221-290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0-145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85-145 kPa.
Center for Injury Biomechanics, Materials and Medicine (CIBM3), Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA.
Vikas
V
Mishra
Center for Injury Biomechanics, Materials and Medicine (CIBM3), Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA.
Maciej
M
Skotak
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, 68198, NE,USA.
Heather
H
Schuetz
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, 68198, NE,USA.
Abi
A
Heller
Center for Injury Biomechanics, Materials and Medicine (CIBM3), Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA.
James
J
Haorah
Center for Injury Biomechanics, Materials and Medicine (CIBM3), Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA.
Namas
N
Chandra
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001753:Blast Injuries / Q000378:metabolism / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001919:Bradycardia / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply; D000070642:Brain Injuries, Traumatic / Q000378:metabolism / Q000473:pathology*; D005107:Explosions; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000073039:Nitrosative Stress; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000447:Aldehydes; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal