title: Factors affecting blast traumatic brain injury.
abstract: The overlapping pathologies and functional outcomes of blast-induced TBI (bTBI) and stress-related neurobehavioral disorders like post-traumatic stress disorder (PTSD) are significant military health issues. Soldiers are exposed to multiple stressors with or without suffering bTBI, making diagnosis and treatment as well as experimental modeling of bTBI a challenge. In this study we compared anxiety levels of Naïve rats to ones that were exposed to each of the following conditions daily for 4 consecutive days: C I: transportation alone; C II: transportation and anesthesia; C III: transportation, anesthesia, and blast sounds; Injured: all three variables plus mild blast overpressure. Following behavioral testing we analyzed sera and select brain regions for protein markers and cellular changes. C I, C II, and C III animals exhibited increased anxiety, but serum corticosterone levels were only significantly elevated in C III and Injured rats. C III and Injured animals also had elevated interferon-γ (IFN-γ) and interleukin-6 (IL-6) levels in the amygdala (AD) and ventral hippocampus (VHC). Glial fibrillary acidic protein (GFAP) levels were only significantly elevated in the VHC, prefrontal cortex (PFC), and AD of Injured animals; they showed an apparent increase in ionized calcium-binding adapter molecule (Iba1) and GFAP immunoreactivity, as well as increased numbers of TUNEL-positive cells in the VHC. Our findings demonstrate that experimental conditions, particularly the exposure to blast acoustics, can increase anxiety and trigger specific behavioral and molecular changes without injury. These findings should be taken into consideration when designing bTBI studies, to better understand the role of stressors in the development of post-traumatic symptoms, and to establish a differential diagnosis for PTSD and bTBI.
authors.affiliation: Department of Anatomy, Physiology and Genetics, the Uniformed Services University, Bethesda, Maryland 20814, USA.
authors.forename: Alaa
authors.initials: A
authors.lastname: Kamnaksh
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Kovesdi
authors.forename: Sook-Kyung
authors.initials: SK
authors.lastname: Kwon
authors.forename: Daniel
authors.initials: D
authors.lastname: Wingo
authors.forename: Farid
authors.initials: F
authors.lastname: Ahmed
authors.forename: Neil E
authors.initials: NE
authors.lastname: Grunberg
authors.forename: Joseph
authors.initials: J
authors.lastname: Long
authors.forename: Denes V
authors.initials: DV
authors.lastname: Agoston
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000523:psychology; D017209:Apoptosis / Q000502:physiology; D001307:Auditory Perception / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D001753:Blast Injuries / Q000473:pathology* / Q000523:psychology*; D001930:Brain Injuries / Q000473:pathology* / Q000523:psychology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D003463:Cues; D005106:Exploratory Behavior / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence
chemical_list: C491049:Aif1 protein, mouse; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D007371:Interferon-gamma; D003345:Corticosterone