Showing papers by "Hua Feng published in 2017"

Endogenous hydrogen sulphide attenuates NLRP3 inflammasome-mediated neuroinflammation by suppressing the P2X7 receptor after intracerebral haemorrhage in rats.

Abstract: Emerging studies have demonstrated the important physiological and pathophysiological roles of hydrogen sulphide (H2S) as a gasotransmitter for NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-associated neuroinflammation in the central nervous system. However, the effects of H2S on neuroinflammation after intracerebral haemorrhage (ICH), especially on the NLRP3 inflammasome, remain unknown. We employed a Sprague–Dawley rat of collagenase-induced ICH in the present study. The time course of H2S content and the spatial expression of cystathionine-β-synthase (CBS) after ICH, the effects of endogenous and exogenous H2S after ICH, the effects of endogenous and exogenous H2S on NLRP3 inflammasome activation under P2X7 receptor (P2X7R) overexpression after ICH, and the involvement of the P2X7R in the mechanism by which microglia-derived H2S prevented NLRP3 inflammasome activation were investigated. We found ICH induced significant downregulation of endogenous H2S production in the brain, which may be the result of decreasing in CBS, the predominant cerebral H2S-generating enzyme. Administration of S-adenosyl-l-methionine (SAM), a CBS-specific agonist, or sodium hydrosulfide (NaHS), a classical exogenous H2S donor, not only restored brain and plasma H2S content but also attenuated brain oedema, microglial accumulation and neurological deficits at 1 day post-ICH by inhibiting the P2X7R/NLRP3 inflammasome cascade. Endogenous H2S production, which was derived mainly by microglia and above treatments, was verified by adenovirus-overexpressed P2X7R and in vitro primary microglia studies. These results indicated endogenous H2S synthesis was impaired after ICH, which plays a pivotal role in the P2X7R/NLRP3 inflammasome-associated neuroinflammatory response in the pathogenesis of secondary brain injury. Maintaining appropriate H2S concentrations in the central nervous system may represent a potential therapeutic strategy for managing post-ICH secondary brain injury and associated neurological deficits.

Role of Glibenclamide in Brain Injury After Intracerebral Hemorrhage.

Abstract: Brain edema following intracerebral hemorrhage (ICH) causes severe secondary brain injury, and no efficient pharmacological preventions are available. The present study was designed to demonstrate the neuroprotective effects of glibenclamide on brain edema and key factors of the blood-brain barrier (BBB). The study was divided into two parts. First, we utilized an autoblood-induced rat model to investigate the expression of sulfonylurea receptor 1 (Sur1). Second, rats were randomized into sham, vehicle, and glibenclamide groups. Neurological scores, brain water content, Evans blue extravasation, Morris water maze test, western blots, and immunofluorescence were used to study the effects of glibenclamide. The expression of the Sur1-Trpm4 channel but not the Sur1-KATP channel was increased in the perihematomal tissue following ICH. Glibenclamide administration significantly decreased the brain water content, restored the BBB, and reduced the expression of MMPs. In addition, glibenclamide improved long-term cognitive deficits following ICH. Glibenclamide protected BBB integrity and improved neurological outcomes after ICH by inhibiting the Sur1-Trpm4 channel, which reduces the expression of MMPs and thereby increases BBB tight-junction protein levels. Glibenclamide may have potential to protect the BBB after ICH.

Cancer stem-like cells can be induced through dedifferentiation under hypoxic conditions in glioma, hepatoma and lung cancer.

Abstract: Traditional studies have shown that transcription factors, including SOX-2, OCT-4, KLF-4, Nanog and Lin-28A, contribute to the dedifferentiation and reprogramming process in normal tissues. Hypoxia is a physiological phenomenon that exists in tumors and promotes the expression of SOX-2, OCT-4, KLF-4, Nanog and Lin-28A. Therefore, an interesting question is whether hypoxia as a stimulating factor promotes the process of dedifferentiation and induces the formation of cancer stem-like cells. Studies have shown that OCT-4 and Nanog overexpression induced the formation of cancer stem cell-like cells through dedifferentiation and enhanced malignancy in lung adenocarcinoma, and reprogramming SOX-2 in pancreatic cancer cells also promoted the dedifferentiation process. Therefore, we investigated this phenomenon in glioma, lung cancer and hepatoma cells and found that the transcription factors mentioned above were highly expressed under hypoxic conditions and induced the formation of spheres, which exhibited asymmetric division and cell cycle arrest. The dedifferentiation process induced by hypoxia highlights a new pattern of cancer development and recurrence, demonstrating that all kinds of cancer cells and the hypoxic microenvironment should be taken into consideration when developing tumor therapies.

Artesunate Protected Blood–Brain Barrier via Sphingosine 1 Phosphate Receptor 1/Phosphatidylinositol 3 Kinase Pathway After Subarachnoid Hemorrhage in Rats

Abstract: Blood–brain barrier preservation plays an important role in attenuating vasogenic brain edema after subarachnoid hemorrhage (SAH). This study was designed to investigate the protective effect and mechanism of artesunate, a traditional anti-malaria drug, on blood–brain barrier after SAH. Three hundred and seventy-seven (377) male Sprague–Dawley rats were subjected to endovascular perforation model for SAH. The rats received artesunate alone or in combination with Sphingosine-1-phosphate receptor-1 (S1P1) small interfering RNA (siRNA), antagonist VPC23019, or phosphatidylinositol 3-kinase inhibitor wortmannin after SAH. Modified Garcia score, SAH grades, brain water content, Evans blue leakage, transmission electron microscope, immunohistochemistry staining, Western blot, and cultured endothelial cells were used to investigate the optimum concentration and the therapeutic mechanism of artesunate. We found that artesunate (200 mg/kg) could do better in raising modified Garcia score, reducing brain water content and Evans blue leakage than other groups after SAH. Moreover, artesunate elevated S1P1 expression, enhanced phosphatidylinositol 3-kinase activation, lowered GSK-3β activation, stabilized β-catenin, and improved the expression of Claudin-3 and Claudin-5 after SAH in rats. These effects were eliminated by S1P1 siRNA, VPC23019, and wortmannin. This study revealed that artesunate could preserve blood–brain barrier integrity and improve neurological outcome after SAH, possibly through activating S1P1, enhancing phosphatidylinositol 3-kinase activation, stabilizing β-catenin via GSK-3β inhibition, and then effectively raising the expression of Claudin-3 and Claudin-5. Therefore, artesunate may be favorable for the blood–brain barrier (BBB) protection after SAH and become a potential candidate for the treatment of SAH patients.

HIF1α regulates single differentiated glioma cell dedifferentiation to stem-like cell phenotypes with high tumorigenic potential under hypoxia.

Abstract: // Pan Wang 1 , Chuan Lan 1 , Shuanglong Xiong 2 , Xiuwen Zhao 1 , You’an Shan 1 , Rong Hu 1 , Wenwu Wan 1 , Shuangjiang Yu 1 , Bin Liao 1 , Guangzhi Li 1 , Junwei Wang 1 , Dewei Zou 1 , Bing Chen 3 , Hua Feng 1 , Nan Wu 1 1 Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China 2 Department of Oncology, Cancer Hospital, Chongqing 400030, China 3 Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China Correspondence to: Nan Wu, email: wunan881@tmmu.edu.cn Keywords: glioblastoma multiforme, hypoxia, dedifferentiation, glioma stem cell, HIF1α Received: April 10, 2016 Accepted: February 20, 2017 Published: March 03, 2017 ABSTRACT The standard treatment for Glioblastoma multiforme (GBM) is surgical resection and subsequent radiotherapy and chemotherapy. Surgical resection of GBM is typically restricted because of its invasive growth, which results in residual tumor cells including glioma stem cells (GSCs) and differentiated cells. Recurrence has been previously thought to occur as a result of these GSCs, and hypoxic microenvironment maintains the GSCs stemness also plays an important role. Summarizing traditional studies and we find many researchers ignored the influence of hypoxia on differentiated cells. We hypothesized that the residual differentiated cells may be dedifferentiated to GSC-like cells under hypoxia and play a crucial role in the rapid, high-frequency recurrence of GBM. Therefore, isolated CD133 – CD15 – NESTIN – cells were prepared as single-cell culture and treated with hypoxia. More than 95% of the surviving single differentiated CD133 – CD15 – NESTIN – cell dedifferentiated into tumorigenic CD133 + CD15 + NESTIN + GSCs, and this process was regulated by hypoxia inducible factor-1α. Moreover, the serum also played an important role in this dedifferentiation. These findings challenge the traditional glioma cell heterogeneity model, cell division model and glioma malignancy development model. Our study also highlights the mechanism of GBM recurrence and the importance of anti-hypoxia therapy. In addition to GSCs, residual differentiated tumor cells also substantially contribute to treatment resistance and the rapid, high recurrence of GBM.

Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage

Abstract: OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor-κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH. CONCLUSIONS This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury.

Abstract: NMDA receptor (NMDAR) is known for its ionotropic function. But recent evidence suggests that NMDAR also has a non-ionotropic property. To determine the role of non-ionotropic activity of NMDARs in clinical relevant conditions, we tested the effect of glycine, a co-agonist of NMDARs, in rat middle cerebral artery occlusion (MCAO), an animal model of cerebral ischemia-reperfusion injury after the animals were injected with the NMDAR channel blocker MK-801 and the glycine receptor antagonist strychnine. We show that glycine reduces the infarct volume in the brain of ischemic stroke animals pre-injected with MK-801 and strychnine. The effect of glycine is sensitive to the antagonist of glycine-GluN1 binding site and blocked by Akt inhibition. In the neurobehavioral tests, glycine improves the functional recovery of stroke animals pre-injected with MK-801 and strychnine. This study suggests that glycine-induced neuroprotection is mediated in part by the non-ionotropic activity of NMDARs via Akt activation in cerebral ischemia-reperfusion injury.

L-Borneol induces transient opening of the blood-brain barrier and enhances the therapeutic effect of cisplatin.

Abstract: The blood-brain barrier (BBB) protects the central nervous system from external insults by limiting substance diffusion through the endothelial interface. The presence of the BBB makes drug delivery in neurological disorders very challenging. Cisplatin has been shown to be cytotoxic to glioma cells, but substantial limitations exist in its clinical applications due to difficulties in penetration across the BBB. Here, we show that L-borneol, a messenger drug widely used in traditional Chinese medicine, can induce transient disruption of the BBB after 20 min of oral administration. The permeability of the BBB began to recover within 1 h of the administration of L-borneol. Different dosages of L-borneol (100, 150, 300, 600, and 900 mg/kg) could induce significant Evans blue leakage (P<0.05). Oral administration of L-borneol elevated cisplatin concentrations in peritumoral tissue (1.24±0.12 μg/g) and tumor loci (1.41±0.13 μg/g), compared with those in the paraffin control (0.88±0.10 and 0.92±0.15 μg/g, respectively) (P<0.05). Furthermore, we found that the median survival period of tumor-bearing mice was significantly higher in the cisplatin plus L-borneol group (24.0±4.9 days) than in the cisplatin plus vehicle group (19.3±3.9 days) (P<0.05). The neurological deficits were more severe in the vehicle and cisplatin plus vehicle groups at 14 and 21 days after implantation of intracranial glioma cells than in the cisplatin plus L-borneol group. In conclusion, our results indicate that the transient opening of the BBB induced by L-borneol could enhance cisplatin accumulation within the glioma tissue and improve the survival of tumor-bearing mice.

White Matter Injury and Recovery after Hypertensive Intracerebral Hemorrhage

Abstract: Hypertensive intracerebral hemorrhage (ICH) could very probably trigger white matter injury in patients. Through the continuous study of white matter injury after hypertensive ICH, we achieve a more profound understanding of the pathophysiological mechanism of its occurrence and development. At the same time, we found a series of drugs and treatment methods for the white matter repair. In the current reality, the research paradigm of white matter injury after hypertensive ICH is relatively obsolete or incomplete, and there are still lots of deficiencies in the research. In the face of the profound changes of stroke research perspective, we believe that the combination of the lenticulostriate artery, nerve nuclei of the hypothalamus-thalamus-basal ganglia, and the white matter fibers located within the capsula interna will be beneficial to the research of white matter injury and repair. This paper has classified and analyzed the study of white matter injury and repair after hypertensive ICH and also rethought the shortcomings of the current research. We hope that it could help researchers further explore and study white matter injury and repair after hypertensive ICH.

Simvastatin Promotes Hematoma Absorption and Reduces Hydrocephalus Following Intraventricular Hemorrhage in Part by Upregulating CD36.

Abstract: We previously found that hematoma worsens hydrocephalus after intraventricular hemorrhage (IVH) via increasing iron deposition and aggravating ependymal cilia injury; therefore, promoting hematoma absorption may be a promising strategy for IVH. Recently, some investigations imply that simvastatin has the ability of accelerating hematoma absorption. Thus, this study was designed to examine the efficacy of simvastatin for IVH in rats. Intracerebral hemorrhage with ventricular extension was induced in adult male Sprague–Dawley rats after autologous blood injection. Simvastatin or vehicle was administered orally at 1 day after IVH and then daily for 1 week. MRI studies were performed to measure the volumes of intracranial hematoma and lateral ventricle at days 1, 3, 7, 14, and 28 after IVH. Motor and neurocognitive functions were assessed at days 1 to 7 and 23 to 28, respectively. Iron deposition, iron-related protein expression, ependymal damage, and histology were detected at day 28. Expression of CD36 scavenger receptor (facilitating phagocytosis) was examined at day 3 after IVH using western blotting and immunofluorescence. Simvastatin significantly increased hematoma absorption ratio, reduced ventricular volume, and attenuated neurological dysfunction post-IVH. In addition, less iron accumulation and more cilia survival was observed in the simvastatin group when compared with the control. What’s more, higher expression of CD36 was detected around the hematoma after simvastatin administration. Simvastatin significantly enhanced brain hematoma absorption, alleviated hydrocephalus, and improved neurological recovery after experimental IVH, which may in part by upregulating CD36 expression. Our data suggest that early simvastatin use may be a novel therapy for IVH patients.

HIF1α regulates glioma chemosensitivity through the transformation between differentiation and dedifferentiation in various oxygen levels

Abstract: Chemotherapy plays a significant role in glioma treatment; however, it has limited effectiveness in extending the life expectancies of glioma patients. Traditional studies have attributed this lack of efficacy to glioma stem cells (GSCs) and their high resistance to chemotherapy, and hypoxia worsens this issue. In contrast, hyperoxia effectively alleviates hypoxia in glioma and sensitizes glioma cells to chemotherapy. In a summary of traditional studies, the majority of researchers overlooked the influence of hypoxia on differentiated cells because they only focused on the maintenance of GSCs stemness, which thus resulted in chemoresistance. Because of this background, we hypothesized that GSCs may be induced through dedifferentiation under hypoxic conditions, and hypoxia maintains GSCs stemness, which thus leads to resistance to chemotherapy. In contrast, hyperoxia inhibits the dedifferentiation process and promotes GSCs differentiation, which increases the sensitization of glioma cells to chemotherapy. Hypoxia-inducible factor-1α (HIF1α) contributes substantially to the stemness maintenance of GSCs and resistance of glioma to chemotherapy; thus, we investigated whether HIF1α regulates the resistance or sensitization of glioma cells to chemotherapy in different oxygen levels. It highlights a novel viewpoint on glioma chemosensitivity from the transformation between dedifferentiation and differentiation in different oxygen levels.

Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke.

Abstract: During the initial stages of hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, the reflex mechanisms are activated to protect cerebral perfusion, but secondary dysfunction of cerebral flow autoregulation will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Evoked by the concept of vascular neural network, the unveiled neural vascular mechanism gains more and more attentions. Astrocyte, neuron, pericyte, endothelium, and so forth are formed as a communicate network to regulate with each other as well as the cerebral blood flow. However, the signaling molecules responsible for this communication between these new players and blood vessels are yet to be definitively confirmed. Recent evidence suggested the pivotal role of transcriptional mechanism, including but not limited to miRNA, lncRNA, exosome, and so forth, for the cerebral blood flow autoregulation. In the present review, we sought to summarize the hemodynamic changes and underline neural vascular mechanism for cerebral blood flow autoregulation in stroke-prone state and after hemorrhagic stroke and hopefully provide more systematic and innovative research interests for the pathophysiology and therapeutic strategies of hemorrhagic stroke.

Terahertz Spectroscopic Diagnosis of Myelin Deficit Brain in Mice and Rhesus Monkey with Chemometric Techniques.

Abstract: While myelin deficit of the central nervous system leads to several severe diseases, the definitive diagnostic means are lacking. We proposed and performed terahertz time-domain spectroscopy (THz-TDS) combined with chemometric techniques to discriminate and evaluate the severity of myelin deficit in mouse and rhesus monkey brains. The THz refractive index and absorption coefficient of paraffin-embedded brain tissues from both normal and mutant dysmyelinating mice are shown. Principal component analysis of time-domain THz signal (PCA-tdTHz) and absorption-refractive index relation of THz spectrum identified myelin deficit without exogenous labeling or any pretreatment. Further, with the established PCA-tdTHz, we evaluated the severity of myelin deficit lesions in rhesus monkey brain induced by experimental autoimmune encephalomyelitis, which is the most-studied animal model of multiple sclerosis. The results well matched the pathological analysis, indicating that PCA-tdTHz is a quick, powerful, evolving tool for identification and evaluation myelin deficit in preclinical animals and potentially in para-clinical human biopsy.

Electromagnetic Fields for the Regulation of Neural Stem Cells.

Abstract: Localized magnetic fields (MFs) could easily penetrate the scalp, skull, and meninges, thus inducing an electrical current in both the central and peripheral nervous systems, which is primarily used in transcranial magnetic stimulation (TMS) for inducing specific effects on different regions or cells that play roles in various brain activities. Studies of repetitive transcranial magnetic stimulation (rTMS) have led to novel attractive therapeutic approaches. Neural stem cells (NSCs) in adult human brain are able to self-renew and possess multidifferential ability to maintain homeostasis and repair damage after acute central nervous system. In the present review, we summarized the electrical activity of NSCs and the fundamental mechanism of electromagnetic fields and their effects on regulating NSC proliferation, differentiation, migration, and maturation. Although it was authorized for the rTMS use in resistant depression patients by US FDA, there are still unveiling mechanism and limitations for rTMS in clinical applications of acute central nervous system injury, especially on NSC regulation as a rehabilitation strategy. More in-depth studies should be performed to provide detailed parameters and mechanisms of rTMS in further studies, making it a powerful tool to treat people who are surviving with acute central nervous system injuries.

Terahertz Imaging Based on Morphological Reconstruction

Abstract: Terahertz (THz) imaging technology is a developing and promising candidate for biological diagnosis, security inspection, and semiconductor wafer examination, due to the low photon energy, the high transparency, and the fingerprint properties of the THz radiation. However, a major encountered bottleneck is the degradation of image quality caused by the power fluctuation of THz source, interference phenomenon, complex environment, and so on. In this paper, we present the mathematical morphology for THz imaging to improve the image quality, taking advantage of morphological reconstructions. Based on the original THz image of a paper with some letters taken from our continuous THz imaging system, the visibility of objects has been successfully enhanced with the suppression of complex background and improvement of peak signal-to-noise ratio using morphological reconstruction. Moreover, morphological reconstruction with proper structuring element parameter was then performed to a THz image of fresh rat cerebral tissue. It presents a satisfactory result with clearer edges and suppressions of the interference fringes and noises. It is suggested that THz imaging based on morphological reconstruction opens a pathway towards automatic techniques for denoising, recognitions, and segmentations in THz biomedical imaging.

MicroRNAs as Big Regulators of Neural Stem/Progenitor Cell Proliferation, Differentiation and Migration: A Potential Treatment for Stroke.

Abstract: Background: Neural stem/progenitor cells (NSPCs)-based treatment is a potential therapeutic approach for stroke. MicroRNAs (miRNAs) have been recently verified as promoters or suppressors in the regulation of NSPCs. However, the underlying mechanisms regulating cell biological behaviors of NSPCs remain largely unknown. Methods: we retrieved papers focusing on potential roles and mechanisms of miRNAs in the regulation of NSPCs, and paid a special attention to clinical therapeutic potentials of miRNAs in stroke patients. This narrative review provides a comprehensive and critical landscape of this issue. Results: We summarize the most recent studies on the roles and mechanisms of miRNAs in regulating the proliferation, differentiation and migration of NSPCs and fully discuss the potential clinical implications of miRNAs interacting with NSPCs in stroke patients. Conclusion: Promising but full of hurdles, miRNAs have been confirmed to play a critical role in regulating NSPCs. Clinical potentials of miRNAs are huge in treating stroke patients receiving NSPCs-based therapy, which can be used as biomarkers for the diagnosis and prognosis, and as targets for controlling the proliferation, differentiation and migration of NSPCs.

Oxiracetam or fastigial nucleus stimulation reduces cognitive injury at high altitude.

Abstract: Background Cognitive impairment is common in people travelling to high altitude. Oxiracetam and electrical stimulation of cerebellar fastigial nucleus may have beneficial impacts. This study was to investigate the effects of preconditioning with Oxiracetam or fastigial nucleus stimulation (FNS) on cognitive decline following the ascension to high altitude. Methods The study was conducted on 60 male military voluntary members who were divided into control group, Oxiracetam group, and fastigial nucleus stimulation group. Transcranial doppler sonography, auditory evoked potential, electroencephalogram (EEG), and cognitive assessments were performed. Results People could still suffer cognitive dysfunction at 4,000 m high altitude despite that they have lived at 1,800 m altitude for several years. The 4,000 m altitude environment also prolonged P300 and N200 latencies. Both Oxiracetam and FNS improved cognitive function, reduced the prolonged latencies of Event Related Potentials (P300 and N200), decreased the average velocity of brain arteries, and enhanced EEG power spectral entropy at 4,000 m altitude. Conclusions Neurophysiological evidences suggest the underlying mechanism of cognitive impairments. Both Oxiracetam and FNS can reduce cognitive decline post arrival at high altitude. They could be a potential pretreatment method for cognitive dysfunction resulted from high altitude.

High-sensitivity attenuated total internal reflection continuous-wave terahertz imaging

Abstract: We demonstrate an attenuated total internal reflection imaging system. The surface information of the sample on top of a prism can be acquired by two-dimensionally scanning this prism moving in the vertical plane with horizontally incident continuous terahertz waves at a fixed height. The principles and feasibility of this method are investigated. The effective imaging area on the prism, image resolution and polarization dependence of contrast enhancement and stability improvement are analyzed. Examples including solid agar, distilled water and porcine tissue are presented, demonstrating the method's advantages of high sensitivity and simple sample preparation. The experimental and theoretical results consistently show that p-polarization contributes to enhanced image contrast and more stable intensity of the attenuated total internal reflected signal.

Transcriptional and Genomic Targets of Neural Stem Cells for Functional Recovery after Hemorrhagic Stroke.

Abstract: Hemorrhagic stroke is a life-threatening disease characterized by a sudden rupture of cerebral blood vessels, and it is widely believed that neural cell death occurs after exposure to blood metabolites or subsequently damaged cells. Neural stem cells (NSCs), which maintain neurogenesis and are found in subgranular zone and subventricular zone, are thought to be an endogenous neuroprotective mechanism for these brain injuries. However, due to the complexity of NSCs and their microenvironment, current strategies cannot satisfactorily enhance functional recovery after hemorrhagic stroke. It is well known that transcriptional and genomic pathways play important roles in ensuring the normal functions of NSCs, including proliferation, migration, differentiation, and neural reconnection. Recently, emerging evidence from the use of new technologies such as next-generation sequencing and transcriptome profiling has provided insight into our understanding of genomic function and regulation of NSCs. In the present article, we summarize and present the current data on the control of NSCs at both the transcriptional and genomic levels. Using bioinformatics methods, we sought to predict novel therapeutic targets of endogenous neurogenesis and exogenous NSC transplantation for functional recovery after hemorrhagic stroke, which could also advance our understanding of its pathophysiology.

Lenticulostriate Artery and Lenticulostriate-artery Neural Complex: New Concept for Intracerebral Hemorrhage.

Abstract: Background Spontaneous intracerebral hemorrhage (ICH) is the poorest prognosis of all stroke subtypes with a high mortality and morbidity. Although considerable progress has been made, no intervention is currently available to alter the outcome of patients with ICH, suggesting a new concept directing ICH study is urgently needed. Methods Most ICH occurs in the deep area of the brain, the basal ganglion, whose blood supply is mainly from lenticulostriate arteries (LSAs). Thus, we focus on ICH occurring in this deep brain area. We summarize the structural and functional features of LSAs and the deep brain, and their interactions, which is essential for the pathogenesis, pathophysiology and management of ICH. Results Here, we review the microanatomy, histological characters, hemodynamics and hypertensive pathology of LSAs. Especially, we look into the interactions between LSAs and their surrounding nerve tissues. The unique microanatomic, histological and hemodynamic features of LSAs underpin its high risk of rupture. The interactions between LSAs and the deep brain determine the pathophysiological process of ICH. Conclusion LSAs and the circumferential deep brain are an interactive and mutually affected entity. We propose a new concept called lenticulostriate-artery neural complex (LNC) to integrate the structural, functional and pathological characteristics of this area, which would be a pragmatic paradigm in directing the future basic and clinical studies on ICH.

Targeting Vascular Neural Network in Intracerebral Hemorrhage

Abstract: Background: Intracerebral hemorrhage (ICH) is a common type of stroke associated with high mortality and morbidity Recent randomized controlled trials could not prove that the current strategies are effective at improving the final outcome of the ICH patients Methods: Here we want to explore potential intervention targets for ICH based on the framework of the vascular neural network (VNN) In this review, a brief history of the evolution of stroke pathophysiology from humoral theory to VNN is discussed Results: As current literature on pathophysiology of ICH is mainly focused on neuroprotection, here we want to evolve the central paradigm towards VNN We stress mechanisms of vascular disruption and impaired blood flow harmony, which are clinically relevant but have received less attention in basic research Conclusion: We propose that VNN could be a robust and practical paradigm in both ICH basic research and clinical practice

Establishment of mouse neuron and microglial cell co-cultured models and its action mechanism.

Abstract: // Bo Zhang 1 , Yunfeng Yang 1 , Jun Tang 1 , Yihao Tao 1 , Bing Jiang 1 , Zhi Chen 1 , Hua Feng 1 , Liming Yang 1 and Gang Zhu 1 1 Department of Neurosurgery, Southwest Hospital,Third Military Medical University, Chongqing, China Correspondence to: Liming Yang, email: yangliming212@163.com Gang Zhu, email: gangzhu6666@sina.com Keywords: neuron, microglial cell, OGD, tOGD Received: February 12, 2017 Accepted: April 15, 2017 Published: May 16, 2017 ABSTRACT Objective: The objective of this study is to establish a co-culture model of mouse neurons and microglial cells, and to analyze the mechanism of action of oxygen glucose deprivation (OGD) and transient oxygen glucose deprivation (tOGD) preconditioning cell models. Results: Mouse primary neurons and BV2 microglial cells were successfully cultured, and the OGD and tOGD models were also established. In the co-culture of mouse primary neurons and microglial cells, the cell number of tOGD mouse neurons and microglial cells was larger than the OGD cell number, observed by a microscope. CCK-8 assay result showed that at 1h after treatment, the OD value in the control group is lower compared to all the other three groups ( P < 0.05). The treatment group exhibited the highest OD value among the four groups. The results observed at 5h were consistent with the results at 1 h. Flow cytometry results showed that at 1h after treatment the apoptosis percentages is higher in the control group compared to other three groups ( P < 0.05). Materials and Methods: Mouse brain tissues were collected and primary neurons cells were cultured. In the meantime mouse BV2 microglia cells were cultured. Two types of cells were co-cultured, and OGD and tOGD cell models were established. There were four groups in the experiment: control group (OGD), treatment group (tOGD+OGD), placebo group (tOGD+OGD+saline) and minocycline intervention group (tOGD+OGD+minocycline). CCK-8 kit was used to detect cell viability and flow cytometry was used to detect apoptosis. Conclusions: In this study, mouse primary neurons and microglial cells were co-cultured. The OGD and tOGD models were established successfully. tOGD was able to effectively protect neurons and microglial cells from damage, and inhibit the apoptosis caused by oxygen glucose deprivation.