title: A rodent model of mild traumatic brain blast injury.
abstract: One of the criteria defining mild traumatic brain injury (mTBI) in humans is a loss of consciousness lasting for less than 30 min. mTBI can result in long-term impairment of cognition and behavior. In rats, the length of time it takes a rat to right itself after injury is considered to be an analog for human return to consciousness. This study characterized a rat mild brain blast injury (mBBI) model defined by a righting response reflex time (RRRT) of more than 4 min but less than 10 min. Assessments of motor coordination relying on beam-balance and foot-fault assays and reference memory showed significant impairment in animals exposed to mBBI. This study's hypothesis is that there are inflammatory outcomes to mTBI over time that cause its deleterious effects. For example, mBBI significantly increased brain levels of interleukin (IL)-1β and tumor necrosis factor-α (TNFα) protein. There were significant inflammatory responses in the cortex, hippocampus, thalamus, and amygdala 6 hr after mBBI, as evidenced by increased levels of the inflammatory markers associated with activation of microglia and macrophages, ionized calcium binding adaptor 1 (IBA1), impairment of the blood-brain barrier, and significant neuronal losses. There were significant increases in phosphorylated Tau (p-Tau) levels, a putative precursor to the development of neuroencephalopathy, as early as 6 hr after mBBI in the cortex and the hippocampus but not in the thalamus or the amygdala. There was an apparent correlation between RRRTs and p-Tau protein levels but not IBA1. These results suggest potential therapies for mild blast injuries via blockade of the IL-1β and TNFα receptors.
authors.affiliation: University of Texas Medical Branch, Galveston, Texas.
authors.forename: J R
authors.initials: JR
authors.lastname: Perez-Polo
authors.forename: H C
authors.initials: HC
authors.lastname: Rea
authors.forename: K M
authors.initials: KM
authors.lastname: Johnson
authors.forename: M A
authors.initials: MA
authors.lastname: Parsley
authors.forename: G C
authors.initials: GC
authors.lastname: Unabia
authors.forename: G-Y
authors.initials: GY
authors.lastname: Xu
authors.forename: D
authors.initials: D
authors.lastname: Prough
authors.forename: D S
authors.initials: DS
authors.lastname: DeWitt
authors.forename: H
authors.initials: H
authors.lastname: Spratt
authors.forename: C E
authors.initials: CE
authors.lastname: Hulsebosch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008264:Macrophages / Q000473:pathology; D008569:Memory Disorders / Q000209:etiology*; D017628:Microglia / Q000473:pathology; D009043:Motor Activity / Q000502:physiology; D011596:Psychomotor Disorders / Q000209:etiology*; D051381:Rats; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; D016875:tau Proteins
keywords: cytokines; inflammation; memory; mild traumatic blast brain injury; phosphorylated Tau protein; righting reflex response