Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Xuefu Zhuyu decoction (XFZY) is an effective traditional Chinese medicine to treat TBI. To elucidate its potential molecular mechanism, this study aimed to demonstrate that XFZY functions as an anti-inflammatory agent by inhibiting the PI3K-AKT-mTOR pathway. Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received XFZY (9 g/kg and 18 g/kg), Vehicle group and Sham group were gavaged with equal volumes of saline. The modified neurologic severity score (mNSS) and the Morris water maze test were used to assess neurological deficits. Arachidonic acid (AA) levels in brain tissue were measured using tandem gas chromatography-mass spectrometry. TNF-α and IL-1β levels in injured ipsilateral brain tissue were detected by ELISA. AKT and mTOR expression were measured by western blot analysis. The results indicated that XFZY significantly enhanced spatial memory acquisition. XFZY (especially at a dose of 9 g/kg) markedly reduced the mNSS and levels of AA, TNF-α and IL-1β. Significant downregulation of AKT/mTOR/p70S6K proteins in brain tissues was observed after the administration of XFZY (especially at a dose of 9 g/kg). XFZY may be a promising therapeutic strategy for reducing inflammation in TBI.

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment.

S yStematic reviews and meta-analyses are fundamental tools used to interpret the effectiveness of a treatment across many studies. Recently, the need to conduct systematic reviews and meta-analyses of animal studies modeling clinically relevant problems has been highlighted. 9,13,36 In particular, systematic reviews of animal experiments will allow decisions regarding the design and conduct of subsequent clinical trials to be based on the entirety of the existing evidence that is synthesized in an unbiased manner. Moreover, systematic reviews permit a more objective appraisal of evidence than is allowed by the traditional narrative-style reviews that are more commonly associated with animal research. Traumatic brain injury (TBI), which is the leading cause of long-term disability in children and young adults worldwide, 11 causes a variety of cognitive, emotional, and behavioral problems that can occur either individually or in combination. 20,40 In the US, a case of TBI occurs every 15 seconds, resulting in 1.7 million new head injury victims per year. Each year, on average, these events are responsible for 50,000 deaths, leave 80,000 individuals with permanent disabilities, and cost more than US$77 billion. 34 However, there are no pharmacological treat- Object. Erythropoietin (EPO) shows promise as a neuroprotective agent in animal models of traumatic brain injury (TBI). However, clinical trials of the efficacy of EPO treatment in patients with TBI yield conflicting results. The authors conducted a systematic review and meta-analysis to assess the effect of EPO in experimental animal models of TBI, the goal being to inform the design of future clinical trials.Methods. The authors identified eligible studies by searching PubMed, Web of Science, MEDLINE, Embase, and Google Scholar in October 2013. Data were pooled using the random-effects model, and results were reported in terms of standardized mean difference. Statistical heterogeneity was examined using both I 2 and chi-square tests, and the presence of small study effects was investigated with funnel plots and Egger tests. In-depth analyses were performed for lesion volume and neurobehavioral outcome, and the studies' methodological quality was also evaluated.Results. Of a total of 290 studies, 13 found an effect of EPO on lesion volume and neurobehavioral outcome. Overall, the methodological quality of the studies was poor, and there was evidence of statistical heterogeneity among the publications as well as small-study effects. However, in-depth analyses showed statistically significant findings in favor of a beneficial effect of EPO after TBI.Conclusions. Despite limitations of this systematic review that may have influenced the findings, the authors conclude that EPO might be beneficial in treating experimental TBI in terms of reducing lesion volume and improving neurobehavioral outcome. However, this review also indicates that more well-designed and well-reported animal studies are needed. (http://thejns.org/doi/abs/10.3171/2014.6.JNS132577) KeY Wo...

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