title: Neurobehavioral, cellular, and molecular consequences of single and multiple mild blast exposure.
abstract: Mild traumatic brain injury, caused by the exposure to single or repeated blast overpressure, is a principal concern due to its pathological complexity and neurobehavioral similarities with posttraumatic stress disorder. In this study, we exposed rats to a single or multiple (five total; administered on consecutive days) mild blasts, assessed their behavior at 1 and 16 days postinjury) and performed histological and protein analyses of brains and plasma at an early (2 h) and a late (22 days) termination time point. One day postinjury, multiple-injured (MI) rats showed the least general locomotion and the most depression- and anxiety-related behaviors among the experimental groups; there were no such differences at 16 days. However, at the later time point, both injured groups displayed elevated levels of select protein biomarkers. Histology showed significantly increased numbers of TUNEL+ (terminal-deoxy-transferase-mediated dUTP nick-end labeling)-positive cells in the dorsal and ventral hippocampus (DHC and VHC) of both injured groups as early as 2 h after injury. At 22 days, the increase was limited to the VHC of MI animals. Our findings suggest that the exposure to mild blast overpressure triggers early hippocampal cell death as well as neuronal, glial, and vascular damage that likely contribute to significant, albeit transient increases in depression- and anxiety-related behaviors. However, the severity of the observed pathological changes in MI rats failed to support the hypothesized cumulative effect of repeated injury. We infer that at this blast frequency, a potential conditioning phenomenon counteracts with and reduces the extent of subsequent damage in MI rats.
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University, Bethesda, MD 20814, USA.
authors.forename: Alaa
authors.initials: A
authors.lastname: Kamnaksh
authors.forename: Sook-Kyung
authors.initials: SK
authors.lastname: Kwon
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Kovesdi
authors.forename: Farid
authors.initials: F
authors.lastname: Ahmed
authors.forename: Erin S
authors.initials: ES
authors.lastname: Barry
authors.forename: Neil E
authors.initials: NE
authors.lastname: Grunberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Long
authors.forename: Denes
authors.initials: D
authors.lastname: Agoston
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000378:metabolism; D001753:Blast Injuries / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D020543:Proteome