Journal of neurotrauma
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Journal of neurotrauma · Jul 2018
Sphingosine 1-Phosphate Receptor Subtype 1 as a Therapeutic Target for Brain Trauma.
Traumatic brain injury (TBI) provokes secondary pathological mechanisms, including ischemic and inflammatory processes. The new research in sphingosine 1-phosphate (S1P) receptor modulators has opened the door for an effective mechanism of reducing central nervous system (CNS) inflammatory lesion activity. Thus, the aim of this study was to characterize the immunomodulatory effect of the functional S1PR1 antagonist, siponimod, in phase III clinical trials for autoimmune disorders and of the competitive sphingosine 1-phosphate receptor subtype 1 (S1PR1) antagonist, TASP0277308, in pre-clinical development in an in vivo model of TBI in mice. ⋯ Moreover, these compounds were able to decrease T-cell activation visible by reduction of CD4+ and CD8+, reduce the lesioned area (measured by 2,3,5-triphenyltetrazolium chloride staining), and to preserve tissue architecture, microtubule stability, and neural plasticity. Moreover, our findings provide pre-clinical evidence for the use of low-dose oral S1PR1 antagonists as neuroprotective strategies for TBI and broaden our understanding of the underlying S1PR1-driven neuroinflammatory processes in the pathophysiology of TBI. Altogether, our results showed that blocking the S1PR1 axis is an effective therapeutic strategy to mitigate neuropathological effects engaged in the CNS by TBI.
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Journal of neurotrauma · Jul 2018
Randomized Controlled Trial Multicenter StudyThe Effect of Goreisan on the Prevention of Chronic Subdural Hematoma Recurrence: Multi-Center Randomized Controlled Study.
The relatively high rate of post-operative recurrence in the treatment of chronic subdural hematoma (CSDH) is a significant problem. Goreisan is an herbal medicine that exhibits a hydragogue effect by inhibiting the expression of aquaporins, and its efficacy in preventing post-operative CSDH recurrence has been suggested by several case trials. This multi-center prospective randomized controlled trial was performed to investigate the preventative effect of goreisan on post-operative CSDH recurrence. ⋯ The recurrence rates considering patients of all ages and patients under 75 years old were relatively low in the goreisan group but without a significant difference. The hematoma volume reduction rates showed no significant difference. Based on the results of the present study, a larger-scale study including more cases is necessary in future to confirm the efficacy of goreisan.
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Journal of neurotrauma · Jul 2018
Cognition, Health-Related Quality of Life, and Depression Ten Years after Moderate to Severe Traumatic Brain Injury: A Prospective Cohort Study.
The aim of this study was to evaluate cognitive function 10 years after moderate-severe traumatic brain injury (TBI) and to investigate the associations among cognitive function, depression, and health-related quality of life (HRQoL). In this prospective cohort study, with measurements at 3, 6, 12, 18, 24, 36, and 120 months post-TBI, patients 18-67 years of age (n = 113) with moderate-severe TBI were recruited. Main outcome measures were depression (Center for Epidemiologic Studies-Depression Scale [CES-D]), subjective cognitive functioning (Cognitive Failure Questionnaire [CFQ]), objective cognitive functioning, and HRQoL (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]). ⋯ We did not find strong evidence for associations between depression and objective cognitive functioning in the long term post-TBI. Disease awareness and selective dropping out may play a role in long-term follow-up studies in moderate-severe TBI. More long-term research is needed in this field.
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Journal of neurotrauma · Jul 2018
Mild Blast Injury Produces Acute Changes in Basal Intracellular Calcium Levels and Activity Patterns in Mouse Hippocampal Neurons.
Mild traumatic brain injury (mTBI) represents a serious public health concern. Although much is understood about long-term changes in cell signaling and anatomical pathologies associated with mTBI, little is known about acute changes in neuronal function. Using large scale Ca2+ imaging in vivo, we characterized the intracellular Ca2+ dynamics in thousands of individual hippocampal neurons using a repetitive mild blast injury model in which blasts were directed onto the cranium of unanesthetized mice on two consecutive days. ⋯ Interestingly, the blast-induced changes in basal Ca2+ levels were independent of the changes in the rates of fast Ca2+ transients, suggesting that blasts had heterogeneous effects on different cell populations. Both types of changes recovered after ∼1 h. Together, our results demonstrate that mTBI induced acute, heterogeneous changes in neuronal function, altering intracellular Ca2+ dynamics across different time scales, which may contribute to the initiation of longer-term pathologies.
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Journal of neurotrauma · Jul 2018
Chronic Alterations in Systemic Immune Function after Traumatic Brain Injury.
There is a compelling link between severe brain trauma and immunosuppression in patients with traumatic brain injury (TBI). Although acute changes in the systemic immune compartment have been linked to outcome severity, the long-term consequences of TBI on systemic immune function are unknown. Here, adult male C57Bl/6 mice underwent moderate-level controlled cortical impact (CCI) or sham surgery, and systemic immune function was evaluated at 1, 3, 7, 14, and 60 days post-injury. ⋯ TBI also caused thymic involution, inverted CD4:CD8 ratios, chronic T lymphopenia, greater memory conversion, increased T cell activation, impaired interferon γ induction, and chronically elevated Th1 cytokine and ROS production. Collectively, our in-depth phenotypic and functional analyses demonstrate that TBI induces widespread suppression of innate and adaptive immune responses after TBI. Moreover, at chronic time points, TBI mice exhibit hallmarks of accelerated immune aging, displaying chronic deficits in systemic immune function.