title: A Novel Preclinical Model of Moderate Primary Blast-Induced Traumatic Brain Injury.
abstract: Blast-induced traumatic brain injury (bTBI) is the "signature" injury of the recent Iraq and Afghanistan wars. Here, we present a novel method to induce bTBI using shock wave (SW) lithotripsy. Using a lithotripsy machine, Wistar rats (N = 70; 408.3 ± 93 g) received five SW pulses to the right side of the frontal cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly divided into three study endpoints: 24 h (n = 25), 72 h (n = 19) and 168 h (n = 26). Neurological and behavioral assessments (Garcia's test, beam walking, Rotarod, and elevated plus maze) were performed at the baseline, and further assessments followed at 3, 6, 24, 72, and 168 h post-injury, if applicable. We performed digital subtraction angiography (DSA) to assess presence of cerebral vasospasm due to induced bTBI. Damage to brain tissue was assessed by an overall histological severity (OHS) score based on depth of injury, area of hemorrhage, and extent of axonal injury. Except for beam walking, OHS was significantly correlated with the other three outcome measures with at least one of their assessments during the first 6 h after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6 h post-injury (r(baseline) = -0.75, r(6hrs) = 0.85; p<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168 h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically significant differences at 1 versus 7 d (p<0.05) and 3 versus 7 d (p<0.01). In this study, we successfully established a preclinical rat model of bTBI with characteristics similar to those observed in clinical cases. This new method may be useful for future investigations aimed at understanding bTBI pathophysiology.
authors.affiliation: 1 Department of Neurology, University of Minnesota , Minneapolis, Minnesota.|2 Department of Neurosurgery, University of Minnesota , Minneapolis, Minnesota.|3 Department of Biomedical Engineering, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Afshin A
authors.initials: AA
authors.lastname: Divani
authors.affiliation: 1 Department of Neurology, University of Minnesota , Minneapolis, Minnesota.|4 Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Murphy
authors.affiliation: 4 Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Joyce
authors.initials: J
authors.lastname: Meints
authors.affiliation: 5 Neurosciences Research Center, Tabriz University of Medical Sciences , Tabriz, Iran .|6 Department of Public Health Sciences, Karolinska Institute , Stockholm, Sweden.
authors.forename: Homayoun
authors.initials: H
authors.lastname: Sadeghi-Bazargani
authors.affiliation: 1 Department of Neurology, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Jessica
authors.initials: J
authors.lastname: Nordberg
authors.affiliation: 7 Department of Urology, Cleveland Clinic , Cleveland, Ohio.
authors.forename: Manoj
authors.initials: M
authors.lastname: Monga
authors.affiliation: 2 Department of Neurosurgery, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
authors.affiliation: 1 Department of Neurology, University of Minnesota , Minneapolis, Minnesota.|3 Department of Biomedical Engineering, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Prerana M
authors.initials: PM
authors.lastname: Bhatia
authors.affiliation: 8 Department of Surgery, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Beilman
authors.affiliation: 9 Department of Pathology, University of New Mexico , Albuquerque, New Mexico.
authors.forename: Karen S
authors.initials: KS
authors.lastname: SantaCruz
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D009048:Motor Skills / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020301:Vasospasm, Intracranial / Q000473:pathology / Q000503:physiopathology*
keywords: axonal damage; blast traumatic brain injury; brain injury; functional outcomes; lithotripsy; vasospasm