Video Coding for Machines: Compact Visual Representation Compression for Intelligent Collaborative Analytics.

As an emerging research practice leveraging recent advanced AI techniques, e.g. deep models based prediction and generation, Video Coding for Machines (VCM) is committed to bridging to an extent separate research tracks of video/image compression and feature compression, and attempts to optimize compactness and efficiency jointly from a unified perspective of high accuracy machine vision and full fidelity human vision. With the rapid advances of deep feature representation and visual data compression in mind, in this paper, we summarize VCM methodology and philosophy based on existing academia and industrial efforts. The development of VCM follows a general rate-distortion optimization, and the categorization of key modules or techniques is established including feature-assisted coding, scalable coding, intermediate feature compression/optimization, and machine vision targeted codec, from broader perspectives of vision tasks, analytics resources, etc. From previous works, it is demonstrated that, although existing works attempt to reveal the nature of scalable representation in bits when dealing with machine and human vision tasks, there remains a rare study in the generality of low bit rate representation, and accordingly how to support a variety of visual analytic tasks. Therefore, we investigate a novel visual information compression for the analytics taxonomy problem to strengthen the capability of compact visual representations extracted from multiple tasks for visual analytics. A new perspective of task relationships versus compression is revisited. By keeping in mind the transferability among different machine vision tasks (e.g. high-level semantic and mid-level geometry-related), we aim to support multiple tasks jointly at low bit rates. In particular, to narrow the dimensionality gap between neural network generated features extracted from pixels and a variety of machine vision features/labels (e.g. scene class, segmentation labels), a codebook hyperprior is designed to compress the neural network-generated features. As demonstrated in our experiments, this new hyperprior model is expected to improve feature compression efficiency by estimating the signal entropy more accurately, which enables further investigation of the granularity of abstracting compact features among different tasks.

Systematic Review and Meta-Analysis of Transradial Access for Carotid Artery Stenting.

There is an increasing number of studies on the transradial approach (TRA) for carotid artery stenting. We aimed to summarize the published data on TRA vs the transfemoral approach (TFA). We searched Science Direct, Embase, PubMed, and Web of Science databases for the relevant literature. Primary outcomes included surgical success and cardiovascular and cerebrovascular complication rates; secondary outcomes included the rates of vascular access-related and other complications. We also compared the crossover rate, success rate, and complications between TRA and TFA carotid stenting. This is the first such meta-analysis regarding TRA and TFA. Twenty studies on TRA carotid stenting were included (n = 1300). Among 19 studies, the success rate of TRA carotid stenting was .951 (95% confidence interval [CI]: .926-.975); death rate was .022 (.011-.032); stroke rate was .005 (.001-.008); radial artery occlusion rate was .008 (.003-.013); and forearm hematoma rate was .003 (-.000 to .006). Among 4 studies comparing TRA and TFA, the success rate was lower (odds ratio: .02; 95% CI: .00-.23) and crossover rate was higher (odds ratio: 40.16; 95% CI: 4.41-365.73) with TRA. Thus, transradial neuro-interventional surgery has a lower success rate than TFA.

Astragalus mongholicus Bunge (Fabaceae): Bioactive Compounds and Potential Therapeutic Mechanisms Against Alzheimer's Disease.

Astragalus mongholicus Bunge (Fabaceae) (also known as Astragali radix-AR), a widely used herb by Traditional Chinese Medicine practitioners, possesses a wide range of pharmacological effects, and has been used to treat Alzheimer's disease (AD) historically. Its bioactive compounds are categorized into four families: saponins, flavonoids, polysaccharides, and others. AR's bioactive compounds are effective in managing AD through a variety of mechanisms, including inhibiting Aß production, aggregation and tau hyperphosphorylation, protecting neurons against oxidative stress, neuroinflammation and apoptosis, promoting neural stem cell proliferation and differentiation and ameliorating mitochondrial dysfunction. This review aims to shed light upon the chemical constituents of AR and the mechanisms underlying the therapeutic effect of each compound in manging AD. Also presented are clinical studies which reported successful management of AD with AR and other herbs. These will be helpful for drug development and clinical application of AR to treat AD.

Towards Low Light Enhancement With RAW Images.

In this paper, we make the first benchmark effort to elaborate on the superiority of using RAW images in the low light enhancement and develop a novel alternative route to utilize RAW images in a more flexible and practical way. Inspired by a full consideration on the typical image processing pipeline, we are inspired to develop a new evaluation framework, Factorized Enhancement Model (FEM), which decomposes the properties of RAW images into measurable factors and provides a tool for exploring how properties of RAW images affect the enhancement performance empirically. The empirical benchmark results show that the Linearity of data and Exposure Time recorded in meta-data play the most critical role, which brings distinct performance gains in various measures over the approaches taking the sRGB images as input. With the insights obtained from the benchmark results in mind, a RAW-guiding Exposure Enhancement Network (REENet) is developed, which makes trade-offs between the advantages and inaccessibility of RAW images in real applications in a way of using RAW images only in the training phase. REENet projects sRGB images into linear RAW domains to apply constraints with corresponding RAW images to reduce the difficulty of modeling training. After that, in the testing phase, our REENet does not rely on RAW images. Experimental results demonstrate not only the superiority of REENet to state-of-the-art sRGB-based methods and but also the effectiveness of the RAW guidance and all components.

Learning End-to-End Lossy Image Compression: A Benchmark.

Image compression is one of the most fundamental techniques and commonly used applications in the image and video processing field. Earlier methods built a well-designed pipeline, and efforts were made to improve all modules of the pipeline by handcrafted tuning. Later, tremendous contributions were made, especially when data-driven methods revitalized the domain with their excellent modeling capacities and flexibility in incorporating newly designed modules and constraints. Despite great progress, a systematic benchmark and comprehensive analysis of end-to-end learned image compression methods are lacking. In this paper, we first conduct a comprehensive literature survey of learned image compression methods. The literature is organized based on several aspects to jointly optimize the rate-distortion performance with a neural network, i.e., network architecture, entropy model and rate control. We describe milestones in cutting-edge learned image-compression methods, review a broad range of existing works, and provide insights into their historical development routes. With this survey, the main challenges of image compression methods are revealed, along with opportunities to address the related issues with recent advanced learning methods. This analysis provides an opportunity to take a further step towards higher-efficiency image compression. By introducing a coarse-to-fine hyperprior model for entropy estimation and signal reconstruction, we achieve improved rate-distortion performance, especially on high-resolution images. Extensive benchmark experiments demonstrate the superiority of our model in rate-distortion performance and time complexity on multi-core CPUs and GPUs.

Bridging the Gap Between Computational Photography and Visual Recognition.

What is the current state-of-the-art for image restoration and enhancement applied to degraded images acquired under less than ideal circumstances? Can the application of such algorithms as a pre-processing step improve image interpretability for manual analysis or automatic visual recognition to classify scene content? While there have been important advances in the area of computational photography to restore or enhance the visual quality of an image, the capabilities of such techniques have not always translated in a useful way to visual recognition tasks. Consequently, there is a pressing need for the development of algorithms that are designed for the joint problem of improving visual appearance and recognition, which will be an enabling factor for the deployment of visual recognition tools in many real-world scenarios. To address this, we introduce the UG 2 dataset as a large-scale benchmark composed of video imagery captured under challenging conditions, and two enhancement tasks designed to test algorithmic impact on visual quality and automatic object recognition. Furthermore, we propose a set of metrics to evaluate the joint improvement of such tasks as well as individual algorithmic advances, including a novel psychophysics-based evaluation regime for human assessment and a realistic set of quantitative measures for object recognition performance. We introduce six new algorithms for image restoration or enhancement, which were created as part of the IARPA sponsored UG 2 Challenge workshop held at CVPR 2018. Under the proposed evaluation regime, we present an in-depth analysis of these algorithms and a host of deep learning-based and classic baseline approaches. From the observed results, it is evident that we are in the early days of building a bridge between computational photography and visual recognition, leaving many opportunities for innovation in this area.

Prolonged Soluble Epoxide Hydrolase Reactivity in Brain Endothelial Cells Is Associated with Long Cognitive Deficits in Sepsis.

Sepsis-associated encephalopathy (SAE) is known to cause long-term cognitive deficits which are related to sustained microglial activation, but the mechanisms are unclear. Recently, studies have shown soluble epoxide hydrolase (sEH) affects the chronic cognitive function or participates in long-term neuropsychiatric illness. We hypothesized that sEH may be involved in the long-term cognitive deficits of SAE. Male C57BL/6 mice were subjected to cecal ligation and puncture (CLP) and were administered vehicle or sEH inhibitor TPPU. CLP induced prolonged endothelial sEH reactivity and sustained activation of microglia in close vicinity to blood vessels at 14 days. We also observed that persistent loss of endothelial BBB function at 14 days following CLP. However, TPPU-treated septic mice exhibited improved BBB function and declined neuro-inflammation. We confirmed these beneficial effects in vitro, which indicated TPPU resulted in a significant improvement in IL-1ß-induced loss of BBB integrity on hCMEC/D3 cell monolayers. Animals were also given a behavior test at 14 days after CLP. Mice showed normal basal locomotor activity in the open field compared with sham-operated animals, but performed fewer entries to the center zone, indicating increased anxiety-like behavior as avoidance of the center. TPPU-treated CLP mice showed normal crossing into the center zone during an open-field test and improved recovery of the ability to learn the novel object recognition (NOR) task compared with saline-treated CLP animals. Our data indicated that prolonged sEH reactivity in brain endothelial cells is associated with long cognitive deficits in sepsis. sEHIs such as TPPU can improve the endothelial barrier function and decrease CLP-induced long-term encephalopathy, at least in part, through anti-inflammatory effects.

Omi/HtrA2 Protease Associated Cell Apoptosis Participates in Blood-Brain Barrier Dysfunction.

Background: Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent cell apoptosis, translocating from mitochondria to the cytosol after an apoptotic insult. Our previous study indicated pre-treatment with UCF-101, a specific inhibitor of Omi/HtrA2, could significantly reduce neuronal apoptosis and attenuate sepsis-induced cognitive dysfunction. Various hypotheses involving blood-brain-barrier (BBB) disruption have been proposed to account for sepsis-associated encephalopathy (SAE). Here, we attempted to explore whether interference of Omi/HtrA2 by RNA interference or UCF-101 pre-treatment can improve sepsis-induced disruption of BBB using human cerebral microvascular endothelial cell line (hCMEC/D3) in vitro and if so, to explore mechanisms involved Omi/HtrA2 protease mediates BBB disruption in SAE. Methods: hCMEC/D3 cell monolayers were intervened by different concentrations of LPS (0-50 µg/mL) over experimental period. Pharmacological or gene interventions (by silencing RNA of Omi/HtrA2) were used to study molecular mechanisms involved in sepsis-associated Omi/HtrA2 translocation, cell apoptosis and BBB dysfunction. BBB function was assessed by trans-endothelial electrical resistance (TEER) and permeability to labeled dextrans (FITC-4kDa). Tight junction (TJ) integrity was assessed by immunofluorescence, western blotting and transmission electron microscopic (TEM) analyses. Apoptosis was determined using flow cytometry and TUNEL assay. Mitochondrial membrane potential (MMP) and oxidative stress were also investigated. Results: LPS affects hCMEC/D3 TJ permeability in a concentration- and time-dependent manner. LPS intervention resulted in a significant disruption of BBB, as manifested by decreased TEER (by ~26%) and a parallel increased paracellular permeability to FITC- (4kDa) dextrans through hCMEC/D3 monolayers. The inhibition of Omi/HtrA2 by UCF-101 or Omi/HtrA2 shRNA reduced LPS-induced brain endothelial cell apoptosis, and resulted in significant improvement on LPS-induced BBB disruption as well as decreased occludin, claudin-5 and ZO-1 expressions. Omi/HtrA2 manipulated endothelial cell apoptosis by shifting into cytosol and inducing X-linked inhibitor of apoptosis protein (XIAP) degradation. UCF-101 administration or Omi/HtrA2 shRNA intervention did attenuate the degradation of XIAP, Poly ADP-ribose polymerase (PARP) cleavage, and caspase-3 cleavage. However, only UCF-101 partly prevented the mobilization of Omi/HtrA2 from the mitochondria to the cytosol after LPS intervention. That abrogation of Omi/HtrA2 by UCF-101 or Omi/HtrA2 shRNA resulted in a significant improvement on LPS-induced decrease of MMP. Oxidative stress was significantly increased in the LPS treated group compared to the control or NC-shRNA group. However, abrogation of Omi/HtrA2 by UCF-101 or Omi/HtrA2 shRNA did not significantly improve oxidative injury. Conclusions: Our study indicated an important role of Omi/HtrA2 in manipulating LPS-induced cell apoptosis and BBB integrity by translocating from mitochondria into cytosol in brain endothelial cells. Omi/HtrA2 induced mitochondrial pathway apoptosis, which involves inhibition of an important antiapoptotic protein XIAP and influence on MMP. Therapeutic methods that inhibit Omi/HtrA2 function may provide a novel therapeutic measure to septic encephalopathy.

Vitamin D Improves Intestinal Barrier Function in Cirrhosis Rats by Upregulating Heme Oxygenase-1 Expression.

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile CCl4 (a mixture of pure CCl4 and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)2D3 (0.5 µg/100 g) and the vehicle were administered simultaneously with CCl4 to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in CCl4-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.

Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model of Septic Encephalopathy.

BACKGROUND/AIMS: the pathogenesis of sepsis-associated encephalopathy (SAE) is multifactorial, involving neurotransmitter alterations, inflammatory cytokines, oxidative damage, mitochondrial dysfunction, apoptosis, and other factors. Mitochondria are major producers of reactive oxygen species, resulting in cellular injury. Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent cell death; it is translocated from mitochondria to the cytosol after an apoptotic insult. We previously found that UCF-101, a specific inhibitor of Omi/HtrA2, has neuroprotective effects on cerebral oxidative injury and cognitive impairment in septic rats. In this study, the mechanisms and molecular pathways underlying these effects were investigated. METHODS: Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) or sham-operated laparotomy and were administered vehicle or UCF-101 (10 µmol/kg). The hippocampus was isolated for subsequent analysis. Omi/HtrA2 expression in the mitochondria or cytosol was evaluated by immunofluorescence or western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was utilized to evaluate levels of apoptosis, and western blotting was used to evaluate apoptosis-related proteins, such as cleaved caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP). Tight junction expression was assessed by immunofluorescence and western blotting. Mitochondrial function, inflammatory cytokines, and oxidative stress were also assayed. In addition, a wet/dry method was used to evaluate brain edema and Evans blue extravasation was used to evaluate blood-brain barrier (BBB) integrity. RESULTS: After CLP treatment, the hippocampus exhibited a mild increase in Omi/HtrA2 expression; cytosolic Omi/HtrA2 expression increased significantly, whereas mitochondrial Omi/HtrA2 expression was reduced, indicating that CLP-induced oxidative stress resulted in the translocation of Omi/HtrA2 from mitochondria to the cytosol. Hippocampal cleaved caspase-3, caspase-9, and PARP levels were significantly higher in animals treated with CLP than in sham-operated animals, while XIAP expression was lower. Treatment with UCF-101 prevented the mobilization of Omi/HtrA2 from mitochondria to the cytosol, attenuated XIAP degradation, and decreased cleaved caspase-3, caspase-9, and PARP expression as well as apoptosis. UCF-101 also reversed the decreased mitochondrial complex I, II, and III respiration and the reduced ATP caused by CLP. In addition, UCF-101 treatment resulted in a significant improvement in BBB integrity, as demonstrated by increased occludin, claudin-5, and zonula occludens 1 levels and reduced Evans blue extravasation. No significant effects of UCF-101 on brain edema were found. Inflammatory cytokines and oxidative stress were significantly higher in the CLP-treated group than in the sham-operated group. However, the inhibition of Omi/HtrA2 by UCF-101 significantly alleviated these responses. CONCLUSION: Our data indicated that Omi/ HtrA2 regulates a mitochondria-dependent apoptotic pathway in a murine model of septic encephalopathy. Inhibition of Omi/HtrA2 by UCF-101 leads to neuroprotection by inhibiting the cytosolic translocation of Omi/HtrA2 and antagonizing the caspase-dependent apoptosis pathway. Therapeutic interventions that inhibit Omi/HtrA2 translocation or protease activity may provide a novel method to treat SAE.

Γ-secretase inhibitor DAPT prevents neuronal death and memory impairment in sepsis associated encephalopathy in septic rats.

BACKGROUND: Brain dysfunction is a frequent complication of sepsis, usually defined as sepsis-associated encephalopathy (SAE). Although the Notch signaling pathway has been proven to be involved in both ischemia and neuronal proliferation, its role in SAE is still unknown. Here, the effect of the Notch signaling pathway involved γ-secretase inhibitor DAPT on SAE in septic rats was investigated in a cecal ligation and puncture (CLP) model. METHODS: Fifty-nine Sprague-Dawley rats were randomly divided into four groups, with the septic group receiving the CLP operation. Twenty-four hours after CLP or sham treatment, rats were sacrificed and their hippocampus was harvested for Western blot analysis. TNF-α expression was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Neuronal apoptosis was assessed by TUNEL staining, and neuronal cell death was detected by H&E staining. Finally, a novel object recognition experiment was used to evaluate memory impairment. RESULTS: Our data showed that sepsis can increase the expression of hippocampal Notch receptor intracellular domain (NICD) and poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1), as well as the inflammatory response, neuronal apoptosis, neuronal death, and memory dysfunction in rats. The γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) can significantly decrease the level of NICD and PARP-1, reduce hippocampal neuronal apoptosis and death, attenuate TNF-α release and rescue cognitive impairment caused by CLP. CONCLUSION: The neuroprotective effect of DAPT on neuronal death and memory impairment in septic rats, which could be a new therapeutic approach for treating SAE in the future.

Ucf-101 protects against cerebral oxidative injury and cognitive impairment in septic rat.

BACKGROUND: Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent and caspase-independent cell apoptosis. It has been verified that Omi/HtrA2 is related to apoptosis due to oxidative stress, which may play an important role in the integrity of mitochondria. Ucf-101 is a specific inhibitor of Omi/HtrA2 and it has been demonstrated that Ucf-101 has organ protective effects in a variety of in vitro and in vivo studies. The aim of our study was to examine the neuroprotective effects of Ucf-101 on cerebral oxidative injury and cognitive impairment in septic rats. METHODS: Male Sprague Dawley rats are subjected to cecal ligation and puncture (CLP) or sham-operated laparotomy. Rats were divided into 4 groups: (1) a sham group plus normal saline (10 mL/kg); (2) a sham group plus Ucf-101 (10 umol/kg); (3) CLP plus normal saline (10 mL/kg); and (4) CLP plus Ucf-101 (10 umol/kg). Brain tumor necrosis factor (TNF)-α level, caspase-3 and caspase-9 activities, malondialdehyde (MDA) content and catalase (CAT) activities were examined. TUNEL staining was utilized to evaluate the amount of apoptosis and the cognitive function was evaluated by the MWM test. The study also assessed the clinical scores of animals and the survival time for the 7-day period. RESULTS: CLP resulted in a poor survival rate, evidence of hippocampal oxidative injury, cell apoptosis and cognitive dysfunction as well as elevated TNF-α level and caspases activities, increased weight loss and clinical scores. Ucf-101 pre-treatment could significantly inhibit caspases activities and cell apoptosis, reduce TNF-α and MDA levels, slightly reverse CAT activities in the brain and attenuate this CLP effect on cognitive dysfunction. In addition, the survival rate and survival time was significantly improved by pre-treatment with Ucf-101. CONCLUSIONS: The present results demonstrated that ucf-101 has the neuroprotective effects on cerebral oxidative injury and cognitive impairment in septic rats.

The protective role of oxymatrine on neuronal cell apoptosis in the hemorrhagic rat brain.

ETHNOPHARMACOLOGICAL RELEVANCE: Oxymatrine is extracted from the traditional Chinese herb Sophora flavescens Ait, possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, and has been used for the treatment of chronic viral hepatitis and many other diseases. AIMS OF THE STUDY: This study aimed to investigate the effects of oxymatrine on inflammatory response mediated by Toll-like receptor4 (TLR4) and nuclear factor kappa-B (NF-κB), oxidative injury induced by 12/15 lipoxygenase (12/15-LOX), phosphorylated p38 mitogen activated protein kinase (phosphor-p38 MAPK) and cytosolic phospholipase A2 (cPLA2), and neuronal cell apoptosis in rat brain with intracerebral hemorrhage (ICH). MATERIALS AND METHODS: Wistar rats were treated intraperitoneally with 60 or 120mg/kg of oxymatrine daily for 5 days following ICH. The rats were sacrificed at hour 2, 6, 12, 24, 48, 72, and 120 after ICH. The gene expressions of TLR-4 and NF-κB, the levels of TNF-alpha, interleukin-1beta, interleukin-6, 12/15-LOX, phospho-p38 MAPK and cPLA2, and the number of apoptotic neuronal cells in rat brain were determined. RESULTS: Oxymatrine at 120mg/kg significantly suppressed gene expressions of TLR-4 and NF-κB, decreased levels of TNF-alpha, interleukin-1beta and interleukin-6, inhibited synthesis of 12/15-LOX, phospho-p38 MAPK and cPLA2 protein, and mitigated apoptotic neuronal changes following ICH in rat. CONCLUSION: Oxymatrine at 120mg/kg following ICH inhibits inflammatory responses, oxidative injury, and neuronal cell apoptosis in rats.

Ginkgolide B reduces neuronal cell apoptosis in the traumatic rat brain: possible involvement of toll-like receptor 4 and nuclear factor kappa B pathway.

Ginkgolide B (GB) has been demonstrated to have a variety of pharmacological actions. Accumulating evidence indicates that GB may exert a protective effect on brain injury. The study was designed to investigate the influence of GB on toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB)-dependent inflammatory responses and neuronal cell apoptosis after traumatic brain injury (TBI). Wistar rats were subjected to 5, 10 and 20 mg/kg GB daily for 5 days, intraperitoneally, following TBI. Rats were sacrificed at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after TBI. The administration of 10 and 20 mg/kg GB could significantly (least-significant difference test: p < 0.05) suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of tumour necrosis factor α, interleukin-1ß and interleukin-6, as well as reduce the number of apoptotic neuronal cells in traumatic rat brain tissues, but the administration of 5 mg/kg GB did not (p > 0.05). However, a clear concentration-response relationship was not found. Thus, GB may inhibit TLR-4 and NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after TBI, which may support the use of GB for the treatment of TBI.

Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgolide B (GB) is one of the ginkgolides that have been isolated from leaves and root bark of the Chinese tree Ginkgo biloba L. (Ginkgoaceae), and is a specific and potent antagonist of platelet activating factor. There is a large body of data showing that GB possesses a markedly neuroprotective property against ischemia-induced impairment in vivo and in vitro. Recently it has been found that GB can inhibit the inflammation in the rat brain tissues with ischemia/reperfusion injury and in the astrocytes treated with lipopolysaccharide, as well as protect neurons against beta-amyloid 25-35 and ischemia-induced apoptosis. However, there have been few reports on the influence of GB on intracerebral hemorrhage (ICH). This study was to investigate the effects of intraperitoneal GB on neuronal cell apoptosis, inflammatory cytokines and Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway after ICH. MATERIALS AND METHODS: Wistar rats obtained an intraperitoneal injection of 5, 10 and 20mg/kg GB after ICH once a day till day 5. Rats were sacrificed by decapitation at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after ICH. Gene expressions of TLR-4 and NF-κB, concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) as well as number of apoptotic neuronal cells in hemorrhagic rat brain tissues were determined. RESULTS: The administration of 10 and 20mg/kg GB could significantly suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of TNF-α, IL-1ß and IL-6 as well as reduce number of apoptotic neuronal cells in hemorrhagic rat brain tissues by Least-significant Difference test (P<0.05), but the administration of 5mg/kg GB not (P>0.05). However, a clear concentration-response relationship was not found. CONCLUSIONS: GB may inhibit TLR4/NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after ICH, which may support the use of G. biloba extracts for the treatment of ICH.

Oxymatrine reduces neuronal cell apoptosis by inhibiting Toll-like receptor 4/nuclear factor kappa-B-dependent inflammatory responses in traumatic rat brain injury.

OBJECTIVE: To investigate the influence of oxymatrine (OMT) on Toll-like receptor 4 (TLR-4)/nuclear factor kappa-B (NF-κB)-dependent inflammatory responses and neuronal cell apoptosis after traumatic brain injury (TBI). MATERIALS AND METHODS: Wistar rats were given an intraperitoneal injection of 60 or 120 mg/kg OMT after TBI once a day till day 5. Rats were killed by decapitation at hours 2, 6 and 12, and days 1, 2, 3 and 5 after TBI. Gene expressions of TLR-4 and NF-κB, concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) as well as the number of apoptotic neuronal cells in traumatic rat brain tissues were determined. RESULTS: The administration of 120 mg/kg OMT could significantly suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of TNF-α, IL-1ß and IL-6, and reduce the number of apoptotic neuronal cells in traumatic rat brain tissues by the Mann-Whitney U test (P < 0.05), but the administration of 60 mg/kg OMT could not (P > 0.05). CONCLUSION: OMT may inhibit TLR4/NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after TBI.

High S100B levels in cerebrospinal fluid and peripheral blood of patients with acute basal ganglial hemorrhage are associated with poor outcome.

BACKGROUND: S100B is involved in brain injury. This study aimed to determine plasma and cerebral spinal fluid (CSF) levels of S100B in patients with spontaneous intracerebral hemorrhage (ICH), and to correlate S100B levels with Glasgow Coma Scale (GCS) scores, ICH volumes, presence of intraventricular hemorrhage (IVH), and survival rate, and to correlate CSF S100B levels with plasma S100B levels as well as CSF interleukin-1beta (IL-1ß) levels. METHODS: Ten patients with suspicion of subarachnoid hemorrhage and 38 patients with spontaneous basal ganglia hemorrhage were included in the study. Their plasma and CSF samples were collected. The concentrations of IL-1ß in CSF and S100B in plasma and CSF were analyzed by enzyme-linked immunosorbent assay. RESULTS: Plasma or CSF S100B levels in the ICH group were significantly higher than those in the control group (178.7±74.2 versus 63.2±23.0 pg/ml; P<0.001 or 158.1±70.9 versus 1.8±0.7 ng/ml; P<0.001). S100B levels were highly associated with GCS scores, ICH volumes, presence of IVH, and survival rate (all P<0.05). CSF S100B levels were highly associated with plasma S100B levels as well as CSF IL-1ß levels (both P<0.01) in patients with ICH. A receiver operating characteristic curve identified CSF and plasma S100B cutoff levels that predicted 1-week mortality of patients with a high sensitivity and specificity. The areas under curves (AUCs) of GCS scores and ICH volumes were larger than those of CSF and plasma S100B levels, but the differences were not statistically significant (P>0.05). CONCLUSION: High levels of S100B are present in the cerebrospinal fluid and peripheral blood of patients with ICH and may contribute to the inflammatory processes of ICH. The levels of CSF and plasma S100B after spontaneous onset of ICH seem to correlate with clinical outcome in these patients. Increases in peripheral S100B properly reflect brain injury, and plasma S100B level may serve as a useful clinical marker for evaluating the prognosis of ICH.

Time course of plasma leptin concentrations after acute spontaneous basal ganglia hemorrhage.

BACKGROUND: Brain cortex leptin messenger ribonucleic acid (mRNA) expression and serum leptin level are up-regulated in ischemic mouse brain, as well as in rat brain with traumatic brain injury. Elevated leptin plasma levels predict cerebral hemorrhagic stroke independently of traditional risk factors. The goal of this study was to investigate change in plasma leptin level after intracerebral hemorrhage (ICH) and to evaluate its relation with disease outcome. METHODS: Eighty-six patients admitted within 6 hrs after ICH and 30 healthy controls were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Its concentration was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: After ICH, plasma leptin level in patients increased during the 6-hour period immediately, peaked in 24 hours, decreased gradually thereafter, and was substantially higher than that in healthy controls during the 7-day period. Plasma leptin levels were highly associated with initial Glasgow coma scores, ICH volumes, presence of intraventricular hemorrhage, and survival rates (all P < 0.05). A multivariate analysis selected plasma leptin level related to plasma C-reactive protein level (standardized coefficient, 0.293; P = 0.003). A multivariate analysis showed baseline plasma leptin level as a good predictor for 1-week mortality (odds ratio, 1.228; 95% confidence interval, 1.070-1.409; P = 0.003). A receiver operating characteristic curve identified that a baseline plasma leptin level greater than 34.1 ng/mL predicted 1-week mortality of patients with 75.0% sensitivity and 85.2% specificity (P < 0.001). Area under curve of GCS score was statistically significantly larger than that of plasma leptin level (P = 0.035), but ICH volume's area under curve not (P = 0.078). CONCLUSIONS: Increased plasma leptin level is found after ICH and may contribute to inflammatory process of ICH, in association with a poor clinical outcome.

High concentrations of resistin in the peripheral blood of patients with acute basal ganglia hemorrhage are associated with poor outcome.

PURPOSE: Resistin increases in peripheral blood of patients with intracerebral hemorrhage (ICH). We sought to evaluate its relation with disease outcome. MATERIALS AND METHODS: Thirty healthy controls and 86 patients with acute ICH were included. Plasma samples were obtained on admission. Its concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Thirty-two patients (37.2%) died from ICH in a week. The plasma resistin level (24.2 +/- 9.7 ng/mL) in patients was significantly higher than that (8.8 +/- 2.4 ng/mL) in healthy controls after adjustment by age, sex, hypertension, diabetes mellitus, hyperlipidemia, and body mass index using analysis of covariate (F = 9.507, P = .003).A univariate correlation analysis found Glasgow Coma Scale (GCS) score and ICH volume, but a multivariate linear regression only selected GCS score (t = -4.587, P < .001) to be related to plasma resistin level. On a multivariate logistic regression, plasma resistin level (odds ratio = 1.257, 95% confidence interval = 1.058-1.492, P = .009) was an independent variable predicting 1-week mortality. A receiver operating characteristic curve identified that a plasma resistin level greater than 26.3 ng/mL predicted 1-week mortality of patients with 81.2% sensitivity and 81.5% specificity (P < .001). Areas under curves of GCS score and ICH volume were not statistically significantly larger than that of plasma resistin level (P > .05). CONCLUSIONS: Increased resistin level is found after ICH, in association with a poor clinical outcome.

Change in plasma S100B level after acute spontaneous basal ganglia hemorrhage.

S100B has been described as a marker of brain injury. However, not much is known regarding change in plasma S100B and its relation with mortality after spontaneous intracerebral hemorrhage (ICH).Thus, we sought to investigate change in plasma S100B level after ICH and to evaluate its relation with disease outcome. Thirty healthy controls and 86 patients with acute ICH were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5, and 7 after ICH. Its concentration was measured by enzyme-linked immunosorbent assay. After ICH, plasma S100B level in patients increased during the 6-h period immediately, peaked in 24 h, plateaued at day 2, decreased gradually thereafter, and was substantially higher than that in healthy controls during the 7-day period. Plasma S100B levels were highly associated with Glasgow Coma Scale scores, ICH volumes, presences of intraventricular hemorrhage, and survival rates (all P < 0.05). Multivariate analysis showed baseline plasma S100B level as a good predictor for 1-week mortality (odds ratio, 1.046; 95%confidence interval, 1.014 - 1.078; P = 0.004). A receiver operating characteristic curve identified plasma S100B cutoff level (192.5 pg/mL) that predicted 1-week mortality with the high sensitivity (93.8%) and specificity (70.4%) values (P < 0.001). The differences between areas under curves of plasma S100B levels and those of Glasgow Coma Scale scores and ICH volumes were not statistically significant (both P > 0.05). Increased S100B level is found after ICH and may contribute to the inflammatory process of ICH, in association with a poor clinical outcome.