title: Neuropathology and neurobehavioral alterations in a rat model of traumatic brain injury to occupants of vehicles targeted by underbody blasts.
abstract: Many victims of blast-induced traumatic brain injury are occupants of military vehicles targeted by land mines. Recently improved vehicle designs protect these individuals against blast overpressure, leaving acceleration as the main force potentially responsible for brain injury. We recently developed a unique rat model of under-vehicle blast-induced hyperacceleration where exposure to acceleration as low as 50G force results in histopathological evidence of diffuse axonal injury and astrocyte activation, with no evidence of neuronal cell death. This study investigated the effects of much higher blast-induced accelerations (1200 to 2800G) on neuronal cell death, neuro-inflammation, behavioral deficits and mortality. Adult male rats were subjected to this range of accelerations, in the absence of exposure to blast overpressure, and evaluated over 28days for working memory (Y maze) and anxiety (elevated plus maze). In addition, brains obtained from rats at one and seven days post-injury were used for neuropathology and neurochemical assays. Sixty seven percent of rats died soon after being subjected to blasts resulting in 2800G acceleration. All rats exposed to 2400G acceleration survived and exhibited transient deficits in working memory and long-term anxiety like behaviors, while those exposed to 1200 acceleration G force only demonstrated increased anxiety. Behavioral deficits were associated with acute microglia/macrophage activation, increased hippocampal neuronal death, and reduced levels of tight junction- and synapse- associated proteins. Taken together, these results suggest that exposure of rats to high underbody blast-induced G forces results in neurologic injury accompanied by neuronal apoptosis, neuroinflammation and evidence for neurosynaptic alterations.
authors.affiliation: University of Maryland School of Medicine, Department of Anesthesiology, Center for Shock, Trauma, and Anesthesiology Research (STAR), 685 W. Baltimore St., Baltimore, MD 21201, United States. Electronic address: ftchantchou@anes.umm.edu.
authors.forename: Flaubert
authors.initials: F
authors.lastname: Tchantchou
authors.affiliation: University of Maryland School of Engineering, Department of Aerospace Engineering, 1131 Glenn L. Martin Hall, College Park, MD 20742, United States. Electronic address: four@umd.edu.
authors.forename: William L
authors.initials: WL
authors.lastname: Fourney
authors.affiliation: University of Maryland School of Engineering, Department of Aerospace Engineering, 1131 Glenn L. Martin Hall, College Park, MD 20742, United States. Electronic address: uleiste@umd.edu.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Leiste
authors.affiliation: University of Maryland School of Medicine, Department of Anesthesiology, Center for Shock, Trauma, and Anesthesiology Research (STAR), 685 W. Baltimore St., Baltimore, MD 21201, United States. Electronic address: vaughan1009@gmail.com.
authors.forename: Joshua
authors.initials: J
authors.lastname: Vaughan
authors.affiliation: University of Maryland School of Medicine, Department of Anesthesiology, Center for Shock, Trauma, and Anesthesiology Research (STAR), 685 W. Baltimore St., Baltimore, MD 21201, United States. Electronic address: prangghran@anes.umm.edu.
authors.forename: Parisa
authors.initials: P
authors.lastname: Rangghran
authors.affiliation: University of Maryland School of Medicine, Department of Anatomy and Neurobiology, Health Science Facility-2, Room 255, Baltimore, MD 21201, United States. Electronic address: apuche@umaryland.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Puche
authors.affiliation: University of Maryland School of Medicine, Department of Anesthesiology, Center for Shock, Trauma, and Anesthesiology Research (STAR), 685 W. Baltimore St., Baltimore, MD 21201, United States. Electronic address: gfiskum@anes.umm.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Fiskum
mesh_terms: D000054:Acceleration / Q000009:adverse effects; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001753:Blast Injuries / Q000150:complications*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D000070642:Brain Injuries, Traumatic / Q000209:etiology* / Q000401:mortality / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C036763:monocyte-macrophage differentiation antigen; D014841:von Willebrand Factor; D019938:Cyclin D1; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3
keywords: Acceleration; Anxiety; Apoptosis; Inflammation; Synapse