Journal of neurotrauma
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Journal of neurotrauma · Jul 2018
Dimethyl Fumarate Attenuates Neuroinflammation and Neurobehavioral Deficits Induced by Experimental Traumatic Brain Injury.
Traumatic brain injury (TBI) is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory, and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in pre-clinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI). Mice were administered DMF orally at the doses of 1, 10, and 30 mg/kg 1 h and 4 h after CCI. ⋯ Further, DMF treatment up-regulated antioxidant Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor pathway, inducing activation of manganese superoxide dismutase and heme-oxygenase-1 and reducing 4-hydroxy-2-nonenal staining. Also, regulating the NF-κB pathway, DMF treatment decreased the severity of inflammation through a modulation of neuronal nitric oxide synthase, interleukin 1, tumor necrosis factor, cyclooxygenase 2, and myeloperoxidase activity, reducing ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein expression. Our results support the thesis that DMF may be an effective neuroprotectant after brain trauma and warrants further study.
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Journal of neurotrauma · Jul 2018
Nano-Pulsed Laser Therapy Is Neuroprotective in a Rat Model of Blast-Induced Neurotrauma.
We have developed a novel, non-invasive nano-pulsed laser therapy (NPLT) system that combines the benefits of near-infrared laser light (808 nm) and ultrasound (optoacoustic) waves, which are generated with each short laser pulse within the tissue. We tested NPLT in a rat model of blast-induced neurotrauma (BINT) to determine whether transcranial application of NPLT provides neuroprotective effects. The laser pulses were applied on the intact rat head 1 h after injury using a specially developed fiber-optic system. ⋯ Immunofluorescence demonstrated that NPLT inhibited microglia activation and reduced the number of cortical neurons expressing activated caspase-3. NPLT also increased expression of BDNF in the hippocampus and the number of proliferating progenitor cells in the dentate gyrus. Our data demonstrate a neuroprotective effect of NPLT and prompt further studies aimed to develop NPLT as a therapeutic intervention after traumatic brain injury (TBI).
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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 · Jun 2018
Impact of Admission Imaging Findings on Neurological Outcomes in Acute Cervical Traumatic Spinal Cord Injury.
Variable and unpredictable spontaneous recovery can occur after acute cervical traumatic spinal cord injury (tSCI). Despite the critical clinical and interventional trial planning implications of this tSCI feature, baseline measures to predict neurologic recovery accurately are not well defined. In this study, we used data derived from 99 consecutive patients (78 male, 21 female) with acute cervical tSCIs to assess the sensitivity and specificity of various clinical and radiological factors in predicting recovery at one year after injury. ⋯ The BASIC score demonstrated the highest overall predictive value for AIS conversion at one year (AUC 0.94). We conclude that admission intrinsic cord signal findings are robust predictive surrogate markers of neurologic recovery after cervical tSCI. Direct comparison of imaging parameters in this cohort of patients indicates that the BASIC score is the single best acute predictor of the likelihood of AIS conversion.