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.

The closed-head impact model of engineered rotational acceleration (CHIMERA) as an application for traumatic brain injury pre-clinical research: A status report.

Closed-head traumatic brain injury (TBI) is a worldwide concern with increasing prevalence and cost to society. Rotational acceleration is a primary mechanism in TBI that results from tissue strains that give rise to diffuse axonal injury. The Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) was recently introduced as a method for the study of impact acceleration effects in pre-clinical TBI research. This review provides a survey of the published literature implementing the CHIMERA device and describes pathological, imaging, neurophysiological, and behavioral findings. Findings show CHIMERA inflicts damage in white matter tracts as a key area of injury. Behaviorally, repeated studies have shown motor deficits and more chronic cognitive effects after CHIMERA injury. Good progress with model application has been accomplished by investigators attending to what is required for model validation. However, the majority of CHIMERA studies only utilize adult male mice. To further establish this model, more work with female animals and various age groups need to be performed, as well as studies to further establish and standardize methodologies for validation of the models for clinical relevance. Common data elements to standardize the reporting methodology for the CHIMERA literature are suggested.

Sex differences in cued fear responses and parvalbumin cell density in the hippocampus following repetitive concussive brain injuries in C57BL/6J mice.

There is strong evidence to suggest a link between repeated head trauma and cognitive and emotional disorders, and Repetitive concussive brain injuries (rCBI) may also be a risk factor for depression and anxiety disorders. Animal models of brain injury afford the opportunity for controlled study of the effects of injury on functional outcomes. In this study, male and cycling female C57BL/6J mice sustained rCBI (3x) at 24-hr intervals and were tested in a context and cued fear conditioning paradigm, open field (OF), elevated zero maze and tail suspension test. All mice with rCBI showed less freezing behavior than sham control mice during the fear conditioning context test. Injured male, but not female mice also froze less in response to the auditory cue (tone). Injured mice were hyperactive in an OF environment and spent more time in the open quadrants of the elevated zero maze, suggesting decreased anxiety, but there were no differences between injured mice and sham-controls in depressive-like activity on the tail suspension test. Pathologically, injured mice showed increased astrogliosis in the injured cortex and white matter tracts (optic tracts and corpus callosum). There were no changes in the number of parvalbumin-positive interneurons in the cortex or amygdala, but injured male mice had fewer parvalbumin-positive neurons in the hippocampus. Parvalbumin-reactive interneurons of the hippocampus have been previously demonstrated to be involved in hippocampal-cortical interactions required for memory consolidation, and it is possible memory changes in the fear-conditioning paradigm following rCBI are the result of more subtle imbalances in excitation and inhibition both within the amygdala and hippocampus, and between more widespread brain regions that are injured following a diffuse brain injury.

Insomnia in the Military: Application and Effectiveness of Cognitive and Pharmacologic Therapies.

Insomnia is one of the most common complaints of US armed service members. Diagnosis and treatment of insomnia in active duty and veteran populations are often complicated by comorbid disorders experienced by military personnel, such as post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). Cognitive behavioral therapy for insomnia (CBTi), pharmacologic interventions, and alternative therapies are discussed as relevant to their applications within military populations. Future directions in research are suggested.