Meningeal and Visual Pathway Magnetic Resonance Imaging Analysis after Single and Repetitive Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA)-Induced Disruption in Male and Female Mice.

The consequences of forceful rotational acceleration on the central nervous system are not fully understood. While traumatic brain injury (TBI) research primarily has focused on effects related to the brain parenchyma, reports of traumatic meningeal enhancement in TBI patients may possess clinical significance. The objective of this study was to evaluate the meninges and brain for changes in dynamic contrast enhancement (DCE) magnetic resonance imaging (MRI) following closed-head impact model of engineered rotational acceleration (CHIMERA)-induced cerebral insult. Adult male and female mice received one (1 × ; n = 19 CHIMERA, n = 19 Sham) or four (4 × one/day; n = 18 CHIMERA, n = 12 Sham) injuries. Each animal underwent three MRI scans: 1 week before injury, immediately after the final injury, and 1 week post-injury. Compared with baseline readings and measures in sham animals, meningeal DCE in males was increased after single impact and repetitive injury. In female mice, DCE was elevated relative to their baseline level after a single impact. One week after CHIMERA, the meningeal enhancement returned to below baseline for single injured male mice, but compared with uninjured mice remained elevated in both sexes in the multiple impact groups. Pre-DCE meningeal T2-weighted relaxation time was increased only after 1 × CHIMERA in injured mice. Since vision is impaired after CHIMERA, visual pathway regions were analyzed through imaging and glial fibrillary acidic protein (GFAP) histology. Initial DCE in the lateral geniculate nucleus (LGN) and superior colliculus (SC) and T2 increases in the optic tract (OPT) and LGN were observed after injury with decreases in DCE and T2 1 week later. Astrogliosis was apparent in the OPT and SC with increased GFAP staining 7 days post-injury. To our knowledge, this is the first study to examine meningeal integrity after CHIMERA in both male and female rodents. DCE-MRI may serve as a useful approach for pre-clinical models of meningeal injury that will enable further evaluation of the underlying mechanisms.

Translational relevance of fear conditioning in rodent models of mild traumatic brain injury.

Mild traumatic brain injury (mTBI) increases the risk of posttraumatic stress disorder (PTSD) in military populations. Utilizing translationally relevant animal models is imperative for establishing a platform to delineate neurobehavioral deficits common to clinical PTSD that emerge in the months to years following mTBI. Such platforms are required to facilitate preclinical development of novel therapeutics. First, this mini review provides an overview of the incidence of PTSD following mTBI in military service members. Secondly, the translational relevance of fear conditioning paradigms used in conjunction with mTBI in preclinical studies is evaluated. Next, this review addresses an important gap in the current preclinical literature; while incubation of fear has been studied in other areas of research, there are relatively few studies pertaining to the enhancement of cued and contextual fear memory over time following mTBI. Incubation of fear paradigms in conjunction with mTBI are proposed as a novel behavioral approach to advance this critical area of research. Lastly, this review discusses potential neurobiological substrates implicated in altered fear memory post mTBI.