Journal of neurotrauma
-
Journal of neurotrauma · Jan 2018
Elucidating pro-inflammatory cytokine responses following traumatic brain injury in a human stem cell model.
Cytokine mediated inflammation likely plays an important role in secondary pathology after traumatic brain injury (TBI). The aim of this study was to elucidate secondary cytokine responses in an in vitro enriched (>80%) human stem cell-derived neuronal model. We exposed neuronal cultures to pre-determined and clinically relevant pathophysiological levels of tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin-1β (IL-1β), shown to be present in the inflammatory aftermath of TBI. ⋯ Importantly, these patterns are consistent with our in vivo (human) TBI data, thus validating our human stem cell-derived neuronal platform as a clinically useful reductionist model. Our data cumulatively suggest that IL-6 and TNF have direct actions, while the action of IL-1β on human neurons likely occurs indirectly through inflammatory cells. The hESC-derived neurons provide a valuable platform to model cytokine mediated inflammation and can provide important insights into the mechanisms of neuroinflammation after TBI.
-
Journal of neurotrauma · Jan 2018
A multimodal MRI study of recovery of consciousness in severe traumatic brain injury: Preliminary results.
Accurate and reliable assessment of the conscious state of patients with severe traumatic brain injury (TBI) is vital for their future management. The purpose of the present study is to find an effective and accurate magnetic resonance imaging (MRI) method for predicting recovery of consciousness in patients with severe TBI. Multimodal MR techniques, including structural MRI, MR spectroscopy (MRS), diffusion tensor imaging (DTI), were used to evaluate brain damage in 58 patients with severe TBI. ⋯ Compared with the RC group, those in the NRC group had a significantly lower N-acetylaspartate to creatine (NAA/Cr) ratio of pons (1.43 ± 0.54 vs. 1.70 ± 0.42), more fiber lines (1046.3 ± 100.8 vs. 975.6 ± 128.1), less peripheral grey matter (pgrey) (579.23 ± 78.85 vs. 638.23 ± 61.16), lower fractional anisotropy (FA) of fibers (0.42 ± 0.04 vs. 0.45 ± 0.03), older age (43.08 ± 14.61 vs. 30.57 ± 12.89), and higher apparent diffusion coefficient (ADC) of fibers (0.99 ± 0.14 vs. 0.89 ± 0.06); all p < 0.05. Age, pgrey, ADC of fibers, NAA/Cr of pons were selected by logistic regression analysis to predict RC, with p values of 0.033 and 0.031, 0.035, 0.030, respectively. Age, pgrey, ADC of fibers, NAA/Cr of pons are effective indicators in the predictive model of RC.
-
Journal of neurotrauma · Jan 2018
Acute Clinical Predictors of Symptom Recovery in Emergency Department Patients with Uncomplicated Mild Traumatic Brain Injury (mTBI) or Non-TBI Injuries.
There is a subset of patients with mild traumatic brain injury (mTBI) who report persistent symptoms that impair their functioning and quality of life. Being able to predict which patients will experience prolonged symptom recovery would help clinicians target resources for clinical follow-up to those most in need, and would facilitate research to develop precision medicine treatments for mTBI. The purpose of this study was to investigate the predictors of symptom recovery in a prospective sample of emergency department trauma patients with either mTBI or non-mTBI injuries. ⋯ Incorporating self-reported litigation involvement modestly increased prediction further (AUC = 0.80). The results highlight the multifactorial nature of mTBI recovery, and injury recovery more generally, and the need to incorporate a variety of variables to achieve adequate prediction. Further research to improve this model and validate it in new and more diverse trauma samples will be useful to build a neurobiopsychosocial model of recovery that informs treatment development.
-
Journal of neurotrauma · Jan 2018
Acute changes in plasma total Tau levels are independent of subconcussive head impacts in college football players.
Athletes in contact sports sustain repetitive subconcussive head impacts in a brief window, yet neurophysiological sequelae from repetitive subconcussion remain unclear. This prospective longitudinal study examined a relationship between changes in plasma Tau protein levels and subconcussive impact kinematic data in 23 Division I collegiate football players during a series of pre-season practices. Plasma measures for Tau and S100β proteins, symptom scores, and near point of convergence were obtained at pre-season baseline and pre-/post-practices. ⋯ Increases in plasma Tau levels were associated with increases in S100β levels only after the first practice. There were no significant associations between changes in Tau levels, symptom scores, or near point of convergence. These data suggest that the changes in levels of circulating Tau protein were independent of subconcussive head impact exposure, pointing to the possibility that other factors may have played roles in changes in plasma Tau levels.
-
The high rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) diagnoses encountered in recent years by the United States Veterans Affairs Healthcare System have increased public awareness and research investigation into these conditions. In this review, we analyze the neural mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common neuropsychiatric symptoms including anxiety, irritability, insomnia, personality changes, and memory problems, and this overlap complicates diagnostic differentiation. ⋯ These disturbances produce neuronal death and degeneration, axonal injury, and dendritic spine dysregulation and changes in neuronal morphology. In laboratory studies, various forms of pharmacological or psychological treatments are capable of reversing these detrimental processes and promoting axonal repair, dendritic remodeling, and neurocircuitry reorganization, resulting in behavioral and cognitive functional enhancements. Based on these mechanisms, novel neurorestorative therapeutics using anti-inflammatory, antioxidant, and anticonvulsant agents may promote better outcomes for comorbid TBI and PTSD.