Journal of neurotrauma
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Journal of neurotrauma · Feb 2019
Chronic White Matter Degeneration, but No Tau Pathology at One-Year Post-Repetitive Mild Traumatic Brain Injury in a Tau Transgenic Model.
Tau pathology associated with chronic traumatic encephalopathy has been documented in the brains of individuals with a history of repetitive mild traumatic brain injury (r-mTBI). At this stage, the pathobiological role of tau in r-mTBI has not been extensively explored in appropriate pre-clinical models. Here, we describe the acute and chronic behavioral and histopathological effects of single and repetitive mild TBI (five injuries given at 48 h intervals) in young adult (3 months old) hTau mice that express all six isoforms of hTau on a null murine tau background. ⋯ Histopathological analyses revealed that hTau mice developed axonal injury, thinning of the corpus callosum, microgliosis and astrogliosis in the white matter at acute and chronic time points after injury. Tau immunohistochemistry and enzyme-linked immunosorbent assay data suggest, however, only transient, injury-dependent increases in phosphorylated tau in the cerebral cortex beneath the impact site and in the CA1/CA3 subregion of the hippocampus after single or r-mTBI. This study implicates white matter degeneration as a prominent feature of survival from mTBI, while the role of tau pathology in the neuropathological sequelae of TBI remains elusive.
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Journal of neurotrauma · Feb 2019
Immune Response Mediates Cardiac Dysfunction after Traumatic Brain Injury.
Cardiovascular complications are common after traumatic brain injury (TBI) and are associated with increased morbidity and mortality. In this study, we investigated the possible role of the immune system in mediating cardiac dysfunction post-TBI in mice. Adult male C57BL/6J mice were subjected to a TBI model of controlled cortical impact (CCI) with or without splenectomy (n = 20/group). ⋯ TBI induces immune cell infiltration and inflammatory factor expression in the heart as well as cardiac dysfunction. Splenectomy decreases heart inflammation and improves cardiac function after TBI. Immune response may contribute to TBI-induced cardiac dysfunction.
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Journal of neurotrauma · Feb 2019
Chemogenomics Systems Pharmacology Mapping of Potential Drug Targets for Treatment of Traumatic Brain Injury.
Traumatic brain injury (TBI) is associated with high mortality and morbidity. Though the death rate of initial trauma has dramatically decreased, no drug has been developed to effectively limit the progression of the secondary injury caused by TBI. TBI appears to be a predisposing risk factor for Alzheimer's disease (AD), whereas the molecular mechanisms remain unknown. ⋯ In particular, our results indicated that TRPV4, NEUROD1, and HPRT1 were among the top therapeutic target candidates for TBI, which are congruent with literature reports. Our analyses also suggested the strong associations between TBI and AD, as perturbations on AD-related genes, such as APOE, APP, PSEN1, and MAPT, can induce similar gene expression patterns as those of TBI. To the best of our knowledge, this is the first CSP-based gene expression profile analyses for predicting TBI-related drug targets, and the findings could be used to guide the design of new drugs targeting the secondary injury caused by TBI.
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Journal of neurotrauma · Feb 2019
Case ReportsClinical and Neurophysiological Changes after Targeted Intrathecal Injections of Bone Marrow Stem Cells in a C3 Tetraplegic Subject.
High-level quadriplegia is a devastating condition with limited treatment options. Bone marrow derived stem cells (BMSCs) are reported to have immunomodulatory and neurotrophic effects in spinal cord injury (SCI). We report a subject with complete C2 SCI who received three anatomically targeted intrathecal infusions of BMSCs under a single-patient expanded access investigational new drug (IND). ⋯ As a single case, the linkage of the clinical and neurophysiological changes to either natural history or to the BMSC infusions cannot be resolved. Nevertheless, such detailed neurophysiological assessment of high cervical SCI patients is rarely performed. Our findings indicate that electrophysiology studies are sensitive to define both residual connectivity and new plasticity.