Journal of neurotrauma
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Journal of neurotrauma · Jan 2017
Diffusion-derived MRI Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after TBI.
Using magnetic resonance imaging (MRI) and an animal model of traumatic brain injury (TBI), we investigated the capacity and sensitivity of diffusion-derived measures, fractional anisotropy (FA), and diffusion entropy, to longitudinally identify structural plasticity in the injured brain in response to the transplantation of human bone marrow stromal cells (hMSCs). Male Wistar rats (300-350g, n = 30) were subjected to controlled cortical impact TBI. At 6 h or 1 week post-injury, these rats were intravenously injected with 1 mL of saline (at 6 h or 1 week, n = 5/group) or with hMSCs in suspension (∼3 × 106 hMSCs, at 6 h or 1 week, n = 10/group). ⋯ Our data demonstrate that administration of hMSCs after TBI leads to enhanced white matter reorganization particularly along the boundary of contusional lesion, which can be identified by both FA and entropy. Compared with the therapy performed at 1 week post-TBI, cell intervention executed at 6 h expedites the brain remodeling process and results in an earlier functional recovery. Although FA and entropy present a similar capacity to dynamically detect the microstructural changes in the tissue regions with predominant orientation of fiber tracts, entropy exhibits a sensitivity superior to that of FA, in probing the structural alterations in the tissue areas with complex fiber patterns.
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Journal of neurotrauma · Jan 2017
Comparative Study Observational StudyTrauma specific brain abnormalities in suspected mild TBI patients identified in the first 48 hours after injury: a blinded MRI comparative study including suspected acute minor stroke patients.
We assessed the utility of a brief MRI protocol, appropriate for the acute setting, to detect acute traumatic brain injury (TBI) in patients with suspected mild TBI (mTBI) and distinguish traumatic from nontraumatic brain injury by comparing trauma with nontrauma patients. Twenty-two patients with suspected mTBI were included in this exploratory study over a period of 9 months. Median time from injury to MR scanning was 5.4 h (interquartile range 3.6-15.3). ⋯ Nine (47%) of the 19 suspected mTBI patients with a negative CT had findings on MRI. Abnormalities on MRI consistent with trauma were observed most frequently on postcontrast FLAIR (83%) and T2*-weighted (58%) sequences. We demonstrated the ability of a fast MRI protocol to identify trauma-related abnormalities not seen on CT, and differentiate acute trauma from nonspecific chronic disease in a blinded cohort of mTBI patients.
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Journal of neurotrauma · Jan 2017
Variation in PPP3CC genotype is associated with long-term recovery after severe brain injury.
After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). ⋯ The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.
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Journal of neurotrauma · Jan 2017
Multicenter StudyScreening for Post-Traumatic Stress Disorder in a Civilian Emergency Department Population with Traumatic Brain Injury.
Post-traumatic stress disorder (PTSD) is a condition associated with traumatic brain injury (TBI). While the importance of PTSD and TBI among military personnel is widely recognized, there is less awareness of PTSD associated with civilian TBI. We examined the incidence and factors associated with PTSD 6 months post-injury in a civilian emergency department population using measures from the National Institute of Neurological Disorders and Stroke TBI Common Data Elements Outcome Battery. ⋯ Screening positive for PTSD was significantly associated with concurrent functional disability, post-concussive and psychiatric symptomatology, decreased satisfaction with life, and decreased performance in visual processing and mental flexibility. Multi-variable regression showed injury mechanism of assault (odds ratio [OR] 3.59; 95% confidence interval [CI] 1.69-7.63; p = 0.001) and prior psychiatric history (OR 2.56; 95% CI 1.42-4.61; p = 0.002) remained significant predictors of screening positive for PTSD, while education (per year OR 0.88; 95% CI 0.79-0.98; p = 0.021) was associated with decreased odds of PTSD. Standardized data collection and review of pre-injury education, psychiatric history, and injury mechanism during initial hospital presentation can aid in identifying patients with mTBI at risk for developing PTSD symptoms who may benefit from closer follow-up after initial injury care.
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Journal of neurotrauma · Jan 2017
Comparative StudyStrong correlation of genome-wide expression after traumatic brain injury in vitro and in vivo implicates a role for SORLA.
The utility of in vitro models of traumatic brain injury (TBI) depends on their ability to recapitulate the in vivo TBI cascade. In this study, we used a genome-wide approach to compare changes in gene expression at several time points post-injury in both an in vitro model and an in vivo model of TBI. We found a total of 2073 differentially expressed genes in our in vitro model and 877 differentially expressed genes in our in vivo model when compared to noninjured controls. ⋯ We confirmed downregulation of SORLA expression in organotypic hippocampal slice cultures by immunohistochemistry and Western blotting and present preliminary data from human tissue that is consistent with these experimental results. Together, these data suggest that the in vitro model of TBI used in this study strongly recapitulates the in vivo TBI pathobiology and is well suited for future mechanistic or therapeutic studies. The data also suggest the possible involvement of SORLA in the post-traumatic cascade linking TBI to AD.