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  • Nicotinamide riboside rescues angiotensin ‐–induced cerebral small vessel disease in mice
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2020-01-14
    Cheng‐Cheng Li; Wei‐Xiang Chen; Jie Wang; Min Xia; Zheng‐Cai Jia; Chao Guo; Xiao‐Qin Tang; Ming‐Xi Li; Yi Yin; Xin Liu; Hua Feng

    Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated.

    更新日期:2020-01-15
  • Microstructural disruption of the right inferior fronto‐occipital and inferior longitudinal fasciculus contributes to WMH‐related cognitive impairment
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2020-01-04
    Hai‐Feng Chen; Li‐Li Huang; Hui‐Ya Li; Yi Qian; Dan Yang; Zhao Qing; Cai‐Mei Luo; Meng‐Chun Li; Bing Zhang; Yun Xu

    White matter hyperintensity (WMH) is the most common neuroimaging manifestation of cerebral small vessel disease and is related to cognitive dysfunction or dementia. This study aimed to investigate the mechanism and effective indicators to predict WMH‐related cognitive impairment.

    更新日期:2020-01-04
  • New clinical characteristics and novel pathogenic variants of patients with hereditary leukodystrophies
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-29
    Juan‐Juan Xie; Wang Ni; Qiao Wei; Huan Ma; Ge Bai; Ying Shen; Zhi‐Ying Wu

    Leukodystrophies are a group of inherited white matter disorders with clinical, genetic, and imaging heterogeneity, which usually pose a diagnostic challenge for physicians. We aimed to identify new clinical characteristics and novel pathogenic variants of hereditary leukodystrophies in this study.

    更新日期:2019-12-30
  • Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5‐HT2c receptor—NPY pathway
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-27
    Xiao‐Qin Wan; Fan Zeng; Xu‐Feng Huang; He‐Qin Yang; Lan Wang; Yan‐Chuan Shi; Zhi‐Hui Zhang; Shu Lin

    Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated.

    更新日期:2019-12-27
  • Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-23
    Johannes P.J.M. de Munter; Igor Shafarevich; Alexei Liundup; Dmitrii Pavlov; Erik Ch Wolters; Anna Gorlova; Ekaterina Veniaminova; Aleksei Umriukhin; Allan Kalueff; Andrei Svistunov; Boris W. Kramer; Klaus‐Peter Lesch; Tatyana Strekalova

    Mutations in DNA/RNA‐binding factor (fused‐in‐sarcoma) FUS and superoxide dismutase‐1 (SOD‐1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD‐1‐G93A (SOD‐1) and new FUS[1‐359]‐transgenic (FUS‐tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti‐inflammatory treatments were investigated using these mutants.

    更新日期:2019-12-23
  • microRNA cluster MC‐let‐7a‐1~let‐7d promotes autophagy and apoptosis of glioma cells by down‐regulating STAT3
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-23
    Zhuan‐Yi Yang; Ying Wang; Qing Liu; Ming Wu

    Accumulating evidence has highlighted the correlation between microRNAs (miRNAs) and the progression of glioma. However, the role of miR cluster MC‐let‐7a‐1 ~ let‐7d in glioma remains elusive. Thus, the current study aimed to investigate the effect of miR cluster MC‐let‐7a‐1 ~ let‐7d on glioma progression.

    更新日期:2019-12-23
  • Dentate nNOS accounts for stress‐induced 5‐HT1A receptor deficiency: Implication in anxiety behaviors
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-21
    Li‐Juan Zhu; Chu Xu; Jie Ren; Lei Chang; Xian‐Hui Zhu; Nan Sun; Guo‐liang Meng; Meng‐Ying Liu; Jing Zhang; Yuan‐Yuan Li; Yu‐Lin Tang; Qi‐Gang Zhou

    Anxiety is a common disorder with high social burden worldwide. Dysfunction of serotonin‐1A receptor (5‐HT1A receptor) in the dentate gyrus (DG) of the hippocampus has been predominantly implicated in the anxiety behavior. However, the molecular mechanism underlying the deficiency of postsynaptic 5‐HT1A receptor in regulating anxiety behavior remains unclear.

    更新日期:2019-12-21
  • (−)‐Phenserine tartrate (PhenT) as a treatment for traumatic brain injury
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-11
    Nigel H. Greig; Daniela Lecca; Shih‐Chang Hsueh; Carlos Nogueras‐Ortiz; Dimitrios Kapogiannis; David Tweedie; Elliot J. Glotfelty; Robert E. Becker; Yung‐Hsiao Chiang; Barry J. Hoffer

    Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality of both young adults and the elderly, and is a key contributing factor in about 30% of all injury‐associated deaths occurring within the United States of America. Albeit substantial impact has been made to improve our comprehension of the mechanisms that underpin the primary and secondary injury stages initiated by a TBI incident, this knowledge has yet to successfully translate into the development of an effective TBI pharmacological treatment. Developing consent suggests that a TBI can concomitantly trigger multiple TBI‐linked cascades that then progress in parallel and, if correct, the multifactorial nature of TBI would make the discovery of a single effective mechanism‐targeted drug unlikely.

    更新日期:2019-12-13
  • Activated Schwann cells and increased inflammatory cytokines IL‐1β, IL‐6, and TNF‐α in patients' sural nerve are lack of tight relationship with specific sensory disturbances in Parkinson's disease
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-11
    Hui Zhang; Jing Wu; Fei‐Fei Shen; Yong‐Sheng Yuan; Xiao Li; Pan Ji; Lin Zhu; Li Sun; Jian Ding; Qi Niu; Ke‐Zhong Zhang

    Neuroinflammation is one of the most important processes in the pathogenesis of Parkinson's disease (PD). Sensory disturbances are common in patients with PD, but the underlying pathophysiological mechanisms remain unknown. This study aimed to characterize the activation of Schwann cells (SCs) and the increase of expression of inflammatory cytokines IL‐1β, IL‐6, and TNF‐α in the sural nerve of PD, and further explore whether peripheral nerve inflammation is the cause of PD sensory disturbances.

    更新日期:2019-12-13
  • The Sphkl/SlP pathway regulates angiogenesis via NOS/NO synthesis following cerebral ischemia‐reperfusion
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-08
    Man-Hua Lv, Shi Li, Yong‐Jia Jiang, Wei Zhang

    Sphingosine kinase 1 (Sphk1) and the signaling molecule sphingosine‐1‐phosphate (S1P) are known to be key regulators of a variety of important biological processes, such as neovascularization. Nitric oxide (NO) is also known to play a role in vasoactive properties, whether Sphk1/S1P signaling is able to alter angiogenesis in the context of cerebral ischemia‐reperfusion injury (IRI), and whether such activity is linked with NO production, however, remains uncertain.

    更新日期:2019-12-09
  • Remote ischemic conditioning for the treatment of ischemic moyamoya disease
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-08
    Jia‐yue Ding, Shu‐ling Shang, Zhi‐shan Sun, Karam Asmaro, Wei‐li Li, Qi Yang, Yu‐chuan Ding, Xun‐ming Ji, Ran Meng

    This study investigated the safety and efficacy of remote ischemic conditioning (RIC) on ameliorating the sequelae of ischemic moyamoya disease (iMMD).

    更新日期:2019-12-09
  • Integrated analysis of exosomal lncRNA and mRNA expression profiles reveals the involvement of lnc‐MKRN2‐42:1 in the pathogenesis of Parkinson's disease
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-12-08
    Qiao Wang, Chun‐Lei Han, Kai‐Liang Wang, Yun‐Peng Sui, Zhi‐Bao Li, Ning Chen, Shi‐Ying Fan, Michitomo Shimabukuro, Feng Wang, Fan‐Gang Meng

    Parkinson's disease (PD) is a common movement disorder for which diagnosis mainly depends on the medical history and clinical symptoms. Exosomes are now considered an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids, and genetic material. Long noncoding (lnc) RNA in exosomes plays a critical role in many diseases, including neurodegenerative disease.

    更新日期:2019-12-09
  • Aging alters Hv1‐mediated microglial polarization and enhances neuroinflammation after peripheral surgery
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-27
    Zhi‐jing Zhang, Xin‐xun Zheng, Xin‐yun Zhang, Yi Zhang, Bao‐yi Huang, Tao Luo

    Perioperative neurocognitive disorders have been widely recognized as common adverse events after surgical intervention. Aging is one of the most important independent risk factors for worsened cognitive outcome, and this deterioration is linked to exacerbated microglia‐mediated neuroinflammation in the aged brain. Under pathological stimulation, microglia are capable of polarizing toward proinflammatory M1 and anti‐inflammatory M2 phenotypes. In the present study, we examined how aging affects microglial responses and neuroinflammation following peripheral surgery. Adult (2‐3 months) and aged (18 months old) male C57/BL6 mice were subjected to tibial fracture or sham surgery. Aged mice exhibited higher level of tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in the hippocampus. The expression of synaptic protein synaptophysin (SYP) was also markedly reduced in the aged brain after the surgery. Both adult and aged mice showed significant increases in M1 microglial polarization (CD16/32). In contrast, tibial fracture surgery induced a decreased M2 microglial polarization (CD206, Ym1/2, Arg1) in aged brain but enhanced M2 microglial polarization in adult brain. Aged mice have upregulated voltage‐gated proton channel (Hv1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression compared with adult mice. The percentage of CD16/32‐positive M1 microglia colabeling with Hv1 was higher in aged mice after tibial fracture surgery. Thus, Hv1/NADPH oxidase upregulation in the aged brain may shift the dynamic equilibrium of microglial activation toward M1 polarization and exaggerate postoperative neuroinflammatory responses after peripheral surgical intervention.

    更新日期:2019-11-28
  • Rosiglitazone ameliorates tissue plasminogen activator‐induced brain hemorrhage after stroke
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-22
    Yan Li, Zi‐Yu Zhu, Bing‐Wei Lu, Ting‐Ting Huang, Yue‐Man Zhang, Na‐Ying Zhou, Wei Xuan, Zeng‐Ai Chen, Da‐Xiang Wen, Wei‐Feng Yu, Pei‐Ying Li

    Delayed thrombolytic therapy with recombinant tissue plasminogen activator (tPA) may exacerbate blood‐brain barrier (BBB) breakdown after ischemic stroke and lead to catastrophic hemorrhagic transformation (HT). Rosiglitazone(RSG), a widely used antidiabetic drug that activates peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), has been shown to protect against cerebral ischemia through promoting poststroke microglial polarization toward the beneficial anti‐inflammatory phenotype. However, whether RSG can alleviate HT after delayed tPA treatment remains unknown. In this study, we sort to examine the role of RSG on tPA‐induced HT after stroke.

    更新日期:2019-11-22
  • Assessment of three essential tremor genetic loci in sporadic Parkinson's disease in Eastern China
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-21
    Ting Gao, Jiong Wu, Ran Zheng, Yi Fang, Chong‐Yao Jin, Yang Ruan, Jin Cao, Jun Tian, Jia‐Li Pu, Bao‐Rong Zhang

    The aim of this study was to investigate potential genetic overlap between essential tremor and Parkinson's disease in a cohort of 825 subjects from an Eastern Chinese population.

    更新日期:2019-11-22
  • microRNA‐139‐5p confers sensitivity to antiepileptic drugs in refractory epilepsy by inhibition of MRP1
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-21
    Li Wang, Lifang Song, Xiaoyi Chen, Junfang Suo, Yanli Ma, Jinghe Shi, Kai Liu, Guohong Chen

    Drug resistance is an intractable issue urgently needed to be overcome for improving efficiency of antiepileptic drugs in treating refractory epilepsy. microRNAs (miRNAs) have been proved as key regulators and therapeutic targets in epilepsy. Accordingly, the aim of the present study was to identify a novel differentially expressed miRNA which could improve the efficiency of antiepileptic drugs during the treatment of refractory epilepsy.

    更新日期:2019-11-21
  • Brain perivascular macrophages: Recent advances and implications in health and diseases
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-20
    Tuo Yang, Ruiming Guo, Feng Zhang

    Brain perivascular macrophages (PVMs) belong to a distinct population of brain‐resident myeloid cells located within the perivascular space surrounding arterioles and venules. Their characterization depends on the combination of anatomical localization, phagocytic capacity, and molecular markers. Under physiological status, they provide structural and functional support for maintaining brain homeostasis, including facilitation of blood‐brain barrier integrity and lymphatic drainage, and exertion of immune functions such as phagocytosis and antigen presentation. Increasing evidence also implicates their specific roles in diseased brain, ranging from cerebrovascular diseases, Aβ pathologies, infections, and autoimmunity. Collectively, PVMs are key components of the brain‐resident immune system, actively participate in a broad‐spectrum of processes in normal and diseased status. Details of the processes are largely underexplored. Targeting PVMs would lead to new insights and be a promising strategy for a broad array of human diseases.

    更新日期:2019-11-21
  • Sexually dimorphic microglia and ischemic stroke
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-20
    Nadine Kerr, Dalton W. Dietrich, Helen M. Bramlett, Ami P. Raval

    Ischemic stroke kills more women compared with men thus emphasizing a significant sexual dimorphism in ischemic pathophysiological outcomes. However, the mechanisms behind this sexual dimorphism are yet to be fully understood. It is well established that cerebral ischemia activates a variety of inflammatory cascades and that microglia are the primary immune cells of the brain. After ischemic injury, microglia are activated and play a crucial role in progression and resolution of the neuroinflammatory response. In recent years, research has focused on the role that microglia play in this sexual dimorphism that exists in the response to central nervous system (CNS) injury. Evidence suggests that the molecular mechanisms leading to microglial activation and polarization of phenotypes may be influenced by sex, therefore causing a difference in the pro/anti‐inflammatory responses after CNS injury. Here, we review advances highlighting that sex differences in microglia are an important factor in the inflammatory responses that are seen after ischemic injury. We discuss the main differences between microglia in the healthy and diseased developing, adult, and aging brain. We also focus on the dimorphism that exists between males and females in microglial‐induced inflammation and energy metabolism after CNS injury. Finally, we describe how all of the current research and literature regarding sex differences in microglia contribute to the differences in poststroke responses between males and females.

    更新日期:2019-11-20
  • Aquaporin 4 deletion exacerbates brain impairments in a mouse model of chronic sleep disruption
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-31
    Rui Zhang, Yun Liu, Yan Chen, Qian Li, Charles Marshall, Ting Wu, Gang Hu, Ming Xiao

    As a normal physiological process, sleep has recently been shown to facilitate clearance of macromolecular metabolic wastes from the brain via the glymphatic system. The aim of the present study was to investigate pathophysiological roles of astroglial aquaporin 4 (AQP4), a functional regulator of glymphatic clearance, in a mouse model of chronic sleep disruption (SD).

    更新日期:2019-11-18
  • Lower serum interleukin‐22 and interleukin‐35 levels are associated with disease status in neuromyelitis optica spectrum disorders
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-24
    Hong Yang, Lu Han, Yun‐Jia Zhou, Jie Ding, Yu Cai, Rong‐Hua Hong, Yong Hao, De‐Sheng Zhu, Xia‐Feng Shen, Yang‐Tai Guan

    The exact pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) remains unclear. A variety of cytokines are involved, but few studies have been performed to explore the novel roles of interleukin‐22 (IL‐22) and interleukin‐35 (IL‐35) in NMOSD. Therefore, this study was designed to investigate serum levels of IL‐22 and IL‐35, and their correlations with clinical and laboratory characteristics in NMOSD.

    更新日期:2019-11-18
  • Mechanism of dorsal root ganglion stimulation for pain relief in painful diabetic polyneuropathy is not dependent on GABA release in the dorsal horn of the spinal cord
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-23
    Eva Koetsier, Glenn Franken, Jacques Debets, Lonne Heijmans, Sander M.J. van Kuijk, Bengt Linderoth, Elbert A. Joosten, Paolo Maino

    It is hypothesized that dorsal root ganglion stimulation (DRGS), sharing some of the mechanisms of traditional spinal cord stimulation (SCS) of the dorsal columns, induces γ‐aminobutyric acid (GABA) release from interneurons in the spinal dorsal horn.

    更新日期:2019-11-18
  • Ganaxolone enhances microglial clearance activity and promotes remyelination in focal demyelination in the corpus callosum of ovariectomized rats
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-22
    Abdeslam Mouihate, Samah Kalakh

    Experimental studies have shown that the progesterone metabolite, allopregnanolone, is endowed with promyelinating effects. The mechanisms underlying these promyelinating effects are not well understood. Therefore, we explored the impact of allopregnanolone's synthetic analogue, ganaxolone, on remyelination and microglial activation following focal demyelination in the corpus callosum of ovariectomized rats.

    更新日期:2019-11-18
  • Therapeutic effects of hirsutella sinensis on the disease onset and progression of amyotrophic lateral sclerosis in SOD1G93A transgenic mouse model
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-18
    Hai‐Yan Shang, Jing‐Jing Zhang, Zhen‐Fa Fu, Yu‐Fei Liu, Song Li, Sheng Chen, Wei‐Dong Le

    Although the pathophysiology of amyotrophic lateral sclerosis (ALS) is still not completely understood, the deregulated microglia polarization and neuroinflammation have been shown to contribute to the pathogenesis and progression of this disease. In the present study, we aimed to determine whether hirsutella sinensis (HS) could reduce neuroinflammatory and pathological changes in the spinal cord of SOD1G93A model mice of ALS and consequently ameliorate disease onset and progression.

    更新日期:2019-11-18
  • Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-18
    Jia Wang, Jie Zuo, Alafate Wahafu, Mao‐de Wang, Rui‐chun Li, Wan‐fu Xie

    Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recurrence. Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy; however, the median survival of patients with GBM remains poor despite these comprehensive therapies. Therefore, the identification of new prognostic biomarkers is urgently needed to evaluate the malignancy and long‐term outcome of glioma.

    更新日期:2019-11-18
  • Exposure to recurrent hypoglycemia alters hippocampal metabolism in treated streptozotocin‐induced diabetic rats
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-07
    Neelesh Dewan, Vibha Shukla, Ashish K. Rehni, Kevin B. Koronowski, Kyle D. Klingbeil, Holly Stradecki‐Cohan, Timothy J. Garrett, Tatjana Rundek, Miguel A. Perez‐Pinzon, Kunjan R. Dave

    Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose‐lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin‐diabetic rats.

    更新日期:2019-11-18
  • Progressive brain atrophy in Parkinson's disease patients who convert to mild cognitive impairment
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-06
    Cheng Zhou, Xiao‐Jun Guan, Tao Guo, Qiao‐Ling Zeng, Ting Gao, Pei‐Yu Huang, Min Xuan, Quan‐Quan Gu, Xiao‐Jun Xu, Min‐Ming Zhang

    Cognitive impairment is a common symptom in the trajectory of Parkinson's disease (PD). However, the pathological underpinning is not fully known. We aimed to explore the critical structural alterations in the process of cognitive decline and its relationships with the dopaminergic deficit and the level of related cerebrospinal fluid (CSF) proteins.

    更新日期:2019-11-18
  • Effect of exosomes from adipose‐derived stem cells on the apoptosis of Schwann cells in peripheral nerve injury
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-07-06
    Cai‐Yue Liu, Gang Yin, Yi‐Dan Sun, Yao‐Fa Lin, Zheng Xie, Arthur W. English, Qing‐Feng Li, Hao‐Dong Lin

    Recovery after peripheral nerve injury (PNI) is often difficult, and there is no optimal treatment. Schwann cells (SCs) are important for peripheral nerve regeneration, so SC‐targeting treatments have gained importance. Adipose‐derived stem cells (ADSCs) and their exosomes can promote peripheral nerve repair, but their interactions with SCs are unclear.

    更新日期:2019-11-18
  • Alterations of cerebral perfusion and functional brain connectivity in medication‐naïve male adults with attention‐deficit/hyperactivity disorder
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-06-23
    Ya‐Wen Tan, Lu Liu, Yan‐Fei Wang, Hai‐Mei Li, Mei‐Rong Pan, Meng‐Jie Zhao, Fang Huang, Yu‐Feng Wang, Yong He, Xu‐Hong Liao, Qiu‐Jin Qian

    Functional brain abnormalities, including altered cerebral perfusion and functional connectivities, have been illustrated in adults with attention‐deficit/hyperactivity disorder (aADHD). The present study attempted to explore the alterations of cerebral blood flow (CBF) and resting‐state functional connectivity (RSFC) simultaneously to understand the neural mechanisms for adults with ADHD comprehensively.

    更新日期:2019-11-18
  • Sema7A, a brain immune regulator, regulates seizure activity in PTZ‐kindled epileptic rats
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-06-09
    Jing Deng, Tao Xu, Juan Yang, Ke‐Ming Zhang, Qi Li, Xin‐Yuan Yu, Rong Li, Jie Fu, Qian Jiang, Jing‐Xi Ma, Yang‐Mei Chen

    Semaphorin7A (Sema7A) plays an important role in the immunoregulation of the brain. In our study, we aimed to investigate the expression patterns of Sema7A in epilepsy and further explore the roles of Sema7A in the regulation of seizure activity and the inflammatory response in PTZ‐kindled epileptic rats.

    更新日期:2019-11-18
  • Functional study and pathogenicity classification of PRRT2 missense variants in PRRT2‐related disorders
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-05-23
    Shao‐Yun Zhao, Li‐Xi Li, Yu‐Lan Chen, Yi‐Jun Chen, Gong‐Lu Liu, Hai‐Lin Dong, Dian‐Fu Chen, Hong‐Fu Li, Zhi‐Ying Wu

    PRRT2 variants are associated with various paroxysmal disorders. To date, more than 90 PRRT2 variants have been reported in PRRT2‐related disorders. Lack of functional study in majority of missense variants makes their pathogenicity uncertain. We aim to evaluate the clinical significance of PRRT2 missense variants by performing in vitro experiments.

    更新日期:2019-11-18
  • Effect of Fasudil on remyelination following cuprizone‐induced demyelination
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-05-23
    Jing Wang, Ruo‐Xuan Sui, Qiang Miao, Qing Wang, Li‐Juan Song, Jie‐Zhong Yu, Yan‐Hua Li, Bao‐Guo Xiao, Cun‐Gen Ma

    Multiple sclerosis is characterized by demyelination/remyelination, neuroinflammation, and neurodegeneration. Cuprizone (CPZ)‐induced toxic demyelination is an experimental animal model commonly used to study demyelination and remyelination in the central nervous system. Fasudil is one of the most thoroughly studied Rho kinase inhibitors.

    更新日期:2019-11-18
  • Cervical spondylotic internal jugular venous compression syndrome
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-05-22
    Jia‐Yue Ding, Da Zhou, Li‐Qun Pan, Jing‐Yuan Ya, Cheng Liu, Feng Yan, Chun‐Qiu Fan, Yu‐Chuan Ding, Xun‐Ming Ji, Ran Meng

    This study aimed to identify the clinical profiles of cervical spondylosis‐related internal jugular vein stenosis (IJVS) comprehensively.

    更新日期:2019-11-18
  • LncRNA FOXD1‐AS1 acts as a potential oncogenic biomarker in glioma
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-05-17
    Yuan‐Feng Gao, Jun‐Yan Liu, Xiao‐Yuan Mao, Zheng‐Wen He, Tao Zhu, Zhi‐Bin Wang, Xi Li, Ji‐Ye Yin, Wei Zhang, Hong‐Hao Zhou, Zhao‐Qian Liu

    Altered activities of long noncoding RNAs (lncRNAs) have been associated with cancer development, and lncRNA FOXD1‐AS1 (FOXD1‐AS1) is the antisense transcript of the gene encoding for FOXD1, known for its role as an oncogene in several tumor types including glioma. However, the role of FOXD1‐AS1 in the differentiation and progression of glioma is not well known.

    更新日期:2019-11-18
  • Transplantation of Nurr1‐overexpressing neural stem cells and microglia for treating parkinsonian rats
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-05-13
    Yuan Qian, Xiao‐Xiang Chen, Wei Wang, Jun‐Jun Li, Xian‐Peng Wang, Zhi‐Wei Tang, Jiao‐Tian Xu, Hai Lin, Zhi‐Yong Yang, Li‐Yan Li, Xiao‐Bin Song, Jia‐Zhi Guo, Li‐Gong Bian, Lei Zhou, Di Lu, Xing‐Li Deng

    Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment.

    更新日期:2019-11-18
  • Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-04-19
    Chun Il Park, Syung Shick Hwang, Hae Won Kim, Jee In Kang, Sang Hak Lee, Se Joo Kim

    Recent evidence suggests that the opioid system is implicated in the pathophysiology of alcohol use disorder (AUD). We aimed to examine the genetic influence of opioid receptors on susceptibility to AUD and its clinical and psychological characteristics including harmful drinking behavior and various aspects of impulsivity in AUD patients.

    更新日期:2019-11-18
  • Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-04-13
    Zhi‐Wen Liu, Cong Han, Hui Wang, Qian Zhang, Si‐Jie Li, Xiang‐yang Bao, Zheng‐Shan Zhang, Lian Duan

    Previous studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis.

    更新日期:2019-11-18
  • Development and validation of a new score for predicting functional outcome of neurocritically ill patients: The INCNS score
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-04-10
    Qiong Gao, Fang Yuan, Xi‐Ai Yang, Ji‐Wen Zhu, Lu Song, Li‐Jie Bi, Ze‐Yu Jiao, Xiao‐Gang Kang, Fang Yang, Wen Jiang

    To develop and validate a novel score for prediction of 3‐month functional outcome in neurocritically ill patients.

    更新日期:2019-11-18
  • Heterogeneity of microglia and their differential roles in white matter pathology
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-15
    Janice Lee, Gen Hamanaka, Eng H. Lo, Ken Arai

    Microglia are resident immune cells that play multiple roles in central nervous system (CNS) development and disease. Although the classical concept of microglia/macrophage activation is based on a biphasic beneficial‐versus‐deleterious polarization, growing evidence now suggests a much more heterogenous profile of microglial activation that underlie their complex roles in the CNS. To date, the majority of data are focused on microglia in gray matter. However, demyelination is a prominent pathologic finding in a wide range of diseases including multiple sclerosis, Alzheimer's disease, and vascular cognitive impairment and dementia. In this mini‐review, we discuss newly discovered functional subsets of microglia that contribute to white matter response in CNS disease onset and progression. Microglia show different molecular patterns and morphologies depending on disease type and brain region, especially in white matter. Moreover, in later stages of disease, microglia demonstrate unconventional immuno‐regulatory activities such as increased phagocytosis of myelin debris and secretion of trophic factors that stimulate oligodendrocyte lineage cells to facilitate remyelination and disease resolution. Further investigations of these multiple microglia subsets may lead to novel therapeutic approaches to treat white matter pathology in CNS injury and disease.

    更新日期:2019-11-17
  • Altered putamen and cerebellum connectivity among different subtypes of Parkinson's disease
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-15
    Bo Shen, Yang Pan, Xu Jiang, Zhuang Wu, Jun Zhu, Jingde Dong, Wenbin Zhang, Pingyi Xu, Yakang Dai, Yang Gao, Chaoyong Xiao, Li Zhang

    Impairment of basal ganglia (BG)‐thalamo‐cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns of putamen among PD subtypes and healthy control (HC) and explored their clinical significance.

    更新日期:2019-11-15
  • Atlastin‐1 modulates seizure activity and neuronal excitability
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-14
    Xi Lu, Min Yang, Yong Yang, Xue‐Feng Wang

    Epilepsy is a neurological disease, and the main clinical manifestation is recurrent seizures. The exact etiology of epilepsy and the pathogenesis of the disorder are not yet fully understood. Atlastin‐1, a dynamin‐like GTPase, interacts with microtubules and is responsible for vesicle formation, both of which are highly associated with the development of epilepsy. Here, we reported that the expression level of atlastin‐1 protein was reduced in the temporal neocortex of patients with temporal lobe epilepsy and in the hippocampus and adjacent cortex of a pentylenetetrazol‐kindled epileptic mouse model. Cells expressing atlastin‐1 coexpressed the inhibitory synaptic marker GAD67 in the temporal cortex and hippocampus of patients with epilepsy and an epileptic mouse model. The lentivirus‐mediated overexpression of atlastin‐1 protein in the hippocampus of mice suppressed seizure activity in behavioral experiments. Patch‐clamp recordings in the Mg2+‐free epilepsy cell model showed that atlastin‐1 overexpression inhibited neuronal excitability by suppressing the discharge frequency of spontaneous action potentials rather than by changing the passive and active properties of action potentials. Inhibitory synaptic transmission, but not excitatory synaptic currents, increased after atlastin‐1 overexpression. These findings suggest that atlastin‐1 likely contributes to the occurrence and development of epilepsy through inhibitory synaptic transmission.

    更新日期:2019-11-15
  • Rosiglitazone polarizes microglia and protects against pilocarpine‐induced status epilepticus
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-14
    Jing Peng, Kan Wang, Weiwei Xiang, Yan Li, Yong Hao, Yangtai Guan

    Activated microglia have been found in the forebrains and hippocampi of temporal lobe epilepsy (TLE) patients and status epileptic (SE) animal models. The peroxisome proliferator‐activated receptor γ (PPAR γ) agonist rosiglitazone has been shown to prevent microglial activation. However, its role in pilocarpine‐induced status epilepticus remains unknown. We aimed to examine the effect of the PPAR γ agonist rosiglitazone in protecting against pilocarpine‐induced status epileptic resulting from over‐activation and to explore phenotypic changes in microglia as the underlying mechanism.

    更新日期:2019-11-15
  • Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-14
    Meng‐yan Hu, Yin‐yao Lin, Bing‐jun Zhang, Dan‐li Lu, Zheng‐qi Lu, Wei Cai

    Aging and aging‐related CNS diseases are associated with inflammatory status. As an efficient amplifier of immune responses, inflammasome is activated and played detrimental role in aging and aging‐related CNS diseases. Macrophage and microglia display robust inflammasome activation in infectious and sterile inflammation. This review discussed the impact of inflammasome activation in microglia/macrophage on senescence “inflammaging” and aging‐related CNS diseases. The preventive or therapeutic effects of targeting inflammasome on retarding aging process or tackling aging‐related diseases are also discussed.

    更新日期:2019-11-15
  • High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-11
    Yan Zhou, Xuan Wang, Xing Huang, Xu‐Dong Li, Kai Cheng, Hao Yu, Yu‐Jie Zhou, Peng Lv, Xiao‐Bing Jiang

    To evaluate the clinical significance of coatomer protein complex subunit beta 2 (COPB2) in patients with glioma using a bioinformatics analysis.

    更新日期:2019-11-11
  • Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-07
    Wenting Zhang, Jingyan Zhao, Rongrong Wang, Ming Jiang, Qing Ye, Amanda D. Smith, Jun Chen, Yejie Shi

    Blood‐borne monocytes/macrophages infiltrate the brain in massive numbers after ischemic stroke, but their impact on poststroke brain injury and recovery remains elusive. This study examined the transcriptomic changes in monocytes/macrophages after ischemic stroke and the functional implications of these changes, particularly with regards to the contribution of these cells to the phagocytic clearance of dead/dying cells (efferocytosis) in the poststroke brain.

    更新日期:2019-11-07
  • 更新日期:2019-11-01
  • Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti-inflammatory phenotype through STAT3 pathway.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : null
    Zong-Jian Liu,Yuan-Yuan Ran,Shu-Yan Qie,Wei-Jun Gong,Fu-Hai Gao,Zi-Tong Ding,Jia-Ning Xi

    AIMS Microglia and infiltrated macrophages play important roles in inflammatory processes after ischemic stroke. Modulating microglia/macrophage polarization from pro-inflammatory phenotype to anti-inflammatory state has been suggested as a potential therapeutic approach in the treatment of ischemic stroke. Melatonin has been shown to be neuroprotective in experimental stroke models. However, the effect of melatonin on microglia polarization after stroke and underlying mechanisms remain unknown. METHODS In vivo, cerebral ischemia was induced by distal middle cerebral artery occlusion (dMCAO) in C57BL/6J mice. Melatonin was injected intraperitoneally (20 mg/kg) at 0 and 24 hours after ischemia. In vitro, the microglial cell line BV2 was stimulated to the pro-inflammatory state with conditioned media (CM) collected from oxygen-glucose deprivation (OGD) challenged neuronal cell line Neuro-2a (N2a). Real-time PCR was utilized to detect the mRNA expression of microglia phenotype markers. Activation of signal transducer and activator of transcription 3 (STAT3) pathway was determined by Western blot of phosphorylated STAT3 (pSTAT3). A neuron-microglia co-culture system was used to determine whether melatonin can inhibit the neurotoxic effect of pro-inflammatory microglia to post-OGD neurons. RESULTS Melatonin treatment reduced brain infarct and improved neurological functions 3 days after dMCAO, which was accompanied by decreased expression of pro-inflammatory markers and increased expression of anti-inflammatory markers in the ischemic brain. In vitro studies confirmed that melatonin directly inhibited the pro-inflammatory responses in BV2 cells upon exposure to OGD neuron CM. The microglia possessing pro-inflammatory phenotype exacerbated post-OGD N2a cells death, whereas melatonin reduced such neurotoxic effect. Further, melatonin enhanced the otherwise inhibited pSTAT3 expression in BV2 cells treated with OGD neuron CM. STAT3 blockade significantly reduced the effect of melatonin on microglial phenotype shift. CONCLUSION Melatonin treatment ameliorates brain damage at least partially through shifting microglia phenotype from pro-inflammatory to anti-inflammatory polarity in a STAT3-dependent manner.

    更新日期:2019-11-01
  • Neural Progenitor Cells Rptor Ablation Impairs Development but Benefits to Seizure-Induced Behavioral Abnormalities.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2016-09-30
    Ling-Lin Chen,Mei-Ling Wu,Feng Zhu,Jie-Jing Kai,Jing-Yin Dong,Xi-Mei Wu,Ling-Hui Zeng

    AIMS Previous study suggests that mTOR signaling pathway may play an important role in epileptogenesis. The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidities. METHODS Mice with conditional knockout of raptor protein were generated by cross-bred Rptorflox/flox mice with nestin-CRE mice. The expression of raptor protein was analyzed by Western blotting in brain tissue samples. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively. Spontaneous seizures were recorded by EEG-video system. Morris water maze, open field test, and excitability test were used to study the behaviors of Rptor CKO mice. RESULTS As the consequence of deleting Rptor, downstream proteins of raptor in mTORC1 signaling were partly blocked. Rptor CKO mice exhibited decrease in body and brain weight under 7 weeks old and accordingly, cortical layer thickness. After kainic acid (KA)-induced status epilepticus, overactivation of mTORC1 signaling was markedly reversed in Rptor CKO mice. Although low frequency of spontaneous seizure and seldom neuronal cell death were observed in both Rptor CKO and control littermates, KA seizure-induced mossy fiber spouting were attenuated in Rptor CKO mice. Additionally, cognitive-deficit and anxiety-like behavior after KA-induced seizures were partly reversed in Rptor CKO mice. CONCLUSION Loss of the Rptor gene in mice neural progenitor cells affects normal development in young age and may contribute to alleviate KA seizure-induced behavioral abnormalities, suggesting that raptor protein plays an important role in seizure comorbidities.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Histone deacetylases and mood disorders: epigenetic programming in gene-environment interactions.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2010-10-22
    Rodrigo Machado-Vieira,Lobna Ibrahim,Carlos A Zarate

    Epigenetics involves molecular mechanisms related to gene expression independent of DNA sequence, mostly mediated by modification of chromatin histones. It has recently been suggested that these transcriptional changes may be implicated in the pathophysiology of mood disorders. In addition, histone deacetylase (HDAC) inhibitors have been shown to control epigenetic programming associated with the regulation of cognition and behavior, and may reverse dysfunctional epigenetic regulation associated with early life events in preclinical models. In this context, the active and continuous adaptation of chromatin, and the access of gene promoters to transcription factor mechanisms may represent a potential therapeutic target in the treatment of mood disorders such as bipolar disorder (BD) and major depressive disorder (MDD). Notably, the standard mood stabilizer valproate (VPA) has been shown to modulate the epigenome by inhibiting HDACs. However, several potential limitations are associated with this class of agents, including lack of selectivity for specific HDAC isoforms as well as risk of potentially serious side effects. Further studies regarding the potential role of chromatin remodeling in the mechanism of action of antidepressants and mood stabilizers are necessary to clarify the potential role of this class of agents as therapeutics for mood disorders.

    更新日期:2019-11-01
  • Effect of different pulse numbers of transcranial magnetic stimulation on motor cortex excitability: Single-blind, randomized cross-over design.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-07
    Zhi-Ming Tang,Chun-Yu Xuan,Xin Li,Zu-Lin Dou,Yu-Jie Lan,Hong-Mei Wen

    AIMS We aimed to investigate the effect of different pulse numbers of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the motor cortex on cortical excitability in healthy participants. METHODS Fifteen healthy participants received 600 and 1200 pulses of 5-Hz rTMS on separate days in a random order. Stimulation (duration, 2 seconds and interval, 1 seconds) was delivered over the left primary motor cortex for the hand, at 90% of resting motor threshold (rMT). The rMT and motor evoked potential (MEP) were measured before stimulation, and at 0 and 30 minutes after rTMS. RESULTS No significant differences were observed between the two conditions for MEP (P = .919) or rMT (P = .266). Compared with baseline, MEP was increased significantly at 0 (P < .001) and 30 minutes (P < .001) after stimulation. After stimulation, rMT was decreased at 0 minute for the 600 and 1200 pulse conditions (P < .001), but had recovered by 30 minutes (P = .073). CONCLUSION Subthreshold 5-Hz rTMS increased motor cortex excitability in healthy humans. However, the number of pulses may exhibit a ceiling effect in that beyond a certain point, that is, increasing the number of pulses may exhibit no further increase in cortical excitability.

    更新日期:2019-11-01
  • Toward personalized brain stimulation: Advances and challenges.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-11-07
    Hanna Lu,Linda Chiu Wa Lam,Yuping Ning

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • White matter repair and treatment strategy after intracerebral hemorrhage.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-10-04
    Yi-Bin Jiang,Kai-Yan Wei,Xu-Yang Zhang,Hua Feng,Rong Hu

    The predilection site of intracerebral hemorrhage (ICH) is in the basal ganglia, which is rich in white matter (WM) fiber bundles, such as cerebrospinal tract in the internal capsule. ICH induced damage to this area can easily lead to severe neurological dysfunction and affects the prognosis and quality of life of patients. At present, the pathophysiological mechanisms of white matter injury (WMI) after ICH have attracted researchers' attention, but studies on the repair and recovery mechanisms and therapy strategies remain rare. In this review, we mainly summarized the WM recovery and treatment strategies after ICH by updating the WMI-related content by reviewing the latest researches and proposing the bottleneck of the current research.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • 更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-10-05
    Badih J Daou,Sravanthi Koduri,B Gregory Thompson,Neeraj Chaudhary,Aditya S Pandey

    Aneurysmal subarachnoid hemorrhage (aSAH) continues to be associated with significant morbidity and mortality despite advances in care and aneurysm treatment strategies. Cerebral vasospasm continues to be a major source of clinical worsening in patients. We intended to review the clinical and experimental aspects of aSAH and identify strategies that are being evaluated for the treatment of vasospasm. A literature review on aSAH and cerebral vasospasm was performed. Available treatments for aSAH continue to expand as research continues to identify new therapeutic targets. Oral nimodipine is the primary medication used in practice given its neuroprotective properties. Transluminal balloon angioplasty is widely utilized in patients with symptomatic vasospasm and ischemia. Prophylactic "triple-H" therapy, clazosentan, and intraarterial papaverine have fallen out of practice. Trials have not shown strong evidence supporting magnesium or statins. Other calcium channel blockers, milrinone, tirilazad, fasudil, cilostazol, albumin, eicosapentaenoic acid, erythropoietin, corticosteroids, minocycline, deferoxamine, intrathecal thrombolytics, need to be further investigated. Many of the current experimental drugs may have significant roles in the treatment algorithm, and further clinical trials are needed. There is growing evidence supporting that early brain injury in aSAH may lead to significant morbidity and mortality, and this needs to be explored further.

    更新日期:2019-11-01
  • Hemorrhagic stroke-Pathomechanisms of injury and therapeutic options.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2019-10-05
    Neeraj Chaudhary,Aditya S Pandey,Xiaoying Wang,Guohua Xi

    更新日期:2019-11-01
  • Baseline assessment of physical frailty in neurological drug development.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2018-08-28
    Marco Canevelli,Giuseppe Bruno,Nicola Vanacore,Matteo Cesari

    更新日期:2019-11-01
  • Motor neuron disease-like phenotype associated with anti-IgLON5 disease.
    CNS Neurosci. Ther. (IF 3.394) Pub Date : 2018-08-15
    Qing-Qing Tao,Qiao Wei,Shui-Jiang Song,Xin-Zhen Yin

    更新日期:2019-11-01
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