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https://www.readbyqxmd.com/read/29452218/tnf%C3%AE-disrupts-blood-brain-barrier-integrity-to-maintain-prolonged-depressive-like-behavior-in-mice
#1
Yuyan Cheng, Sachi Desse, Ana Martinez, Ryan J Worthen, Richard S Jope, Eleonore Beurel
Recovery from major depressive disorder is difficult, particularly in patients who are refractory to antidepressant treatments. To examine factors that regulate recovery, we developed a prolonged learned helplessness depression model in mice. After the induction of learned helplessness, mice were separated into groups that recovered or did not recover within 4 weeks. Comparisons were made between groups in hippocampal proteins, inflammatory cytokines, and blood brain barrier (BBB) permeability. Compared with mice that recovered and control mice, non-recovered mice displaying prolonged learned helplessness had greater hippocampal activation of glycogen synthase kinase-3 (GSK3), higher levels of tumor necrosis factor-α (TNFα), interleukin-17A, and interleukin-23, increased permeability of the blood brain barrier (BBB), and lower levels of the BBB tight junction proteins occludin, ZO1, and claudin-5...
February 13, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29430654/enhanced-efficacy-of-azd3759-and-radiation-on-brain-metastasis-from-egfr-mutant-non-small-cell-lung-cancer
#2
Xue Li, Yingchun Wang, Jia Wang, Tianwei Zhang, Li Zheng, Zhenfan Yang, Ligang Xing, Jinming Yu
The prognosis of patients with brain metastasis (BM) is poor. In this study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC. Besides, the antitumor activity displayed no difference between radiation concurrently with AZD3759 and radiation sequentially with AZD3759. Mechanistically, we found that two factors determined the enhanced efficacy: cells with EGFRm which were sensitive to AZD3759, and a relative high concentration of AZD3759...
February 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29332257/kynurenic-acid-and-its-derivatives-are-able-to-modulate-the-adhesion-and-locomotion-of-brain-endothelial-cells
#3
Eszter Lajkó, Bernadett Tuka, Ferenc Fülöp, István Krizbai, József Toldi, Kálmán Magyar, László Vécsei, László Kőhidai
The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in several neurodegenerative disorders [characterized by damage to the cerebral endothelium and to the blood-brain barrier (BBB)] are well established. Cell-extracellular matrix (ECM) adhesion is supposedly involved in recovery of impaired cerebral endothelium integrity (endothelial repair). The present work aimed to investigate the effects of KYNA and its synthetic derivatives on cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8 rat brain endothelial cell line, modeling the BBB endothelium...
January 13, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29311672/ephb3-signaling-induces-cortical-endothelial-cell-death-and-disrupts-the-blood-brain-barrier-after-traumatic-brain-injury
#4
Poincyane Assis-Nascimento, Yanina Tsenkina, Daniel J Liebl
Damage to the cerebrovascular network is a major contributor to dysfunction in patients suffering from traumatic brain injury (TBI). Vessels are composed of lumen-forming endothelial cells that associate closely with both glial and neuronal units to establish a functional blood-brain barrier (BBB). Under normal physiological conditions, these vascular units play important roles in central nervous system (CNS) homeostasis by delivering oxygen and nutrients while filtering out molecules and cells that could be harmful; however, after TBI this system is disrupted...
January 8, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29215736/protective-effect-of-epigenetic-silencing-of-cyclind1-against-spinal-cord-injury-using-bone-marrow-derived-mesenchymal-stem-cells-in-rats
#5
Yuan Wang, Qing-Jie Kong, Jin-Chuan Sun, Xi-Ming Xu, Yong Yang, Ning Liu, Jian-Gang Shi
OBJECTIVE: This study focuses on the protective effect of epigenetic silencing of CyclinD1 against spinal cord injury (SCI) using bone marrow-derived mesenchymal stem cells (BMSCs) in rats. METHODS: Eighty-eight adult female Wistar rats were randomly assigned into the sham group, the control group, the si-CyclinD1 + BMSCs group and the BMSCs group. CyclinD1 protein and mRNA expressions after siRNA transfection were detected by western blotting and qRT-PCR. The siRNA-CyclinD1 BMSCs were transplanted into rats in the si-CyclinD1 + BMSCs group using stereotaxic method 6 h after SCI...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29133510/single-cell-immuno-laser-microdissection-coupled-to-label-free-proteomics-to-reveal-the-proteotypes-of-human-brain-cells-after-ischemia
#6
Teresa García-Berrocoso, Víctor Llombart, Laura Colàs-Campàs, Alexandre Hainard, Virginie Licker, Anna Penalba, Laura Ramiro, Alba Simats, Alejandro Bustamante, Elena Martínez-Saez, Francesc Canals, Jean-Charles Sanchez, Joan Montaner
Cerebral ischemia entails rapid tissue damage in the affected brain area causing devastating neurological dysfunction. How each component of the neurovascular unit contributes or responds to the ischemic insult in the context of the human brain has not been solved yet. Thus, the analysis of the proteome is a straightforward approach to unraveling these cell proteotypes.In this study, post-mortem brain slices from ischemic stroke patients were obtained corresponding to infarcted (IC) and contralateral (CL) areas...
November 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29115923/neuroprotective-effect-of-neuroserpin-in-non-tpa-induced-intracerebral-hemorrhage-mouse-models
#7
Wei Li, Tetsuya Asakawa, Sha Han, Baoguo Xiao, Hiroki Namba, Chuanzhen Lu, Qiang Dong, Liang Wang
BACKGROUND: The neuroprotective effects of neuroserpin (NSP) have been well documented in both patients and animal models with cerebral ischemia; however, have never been investigated in hemorrhagic stroke. The aim of this study is to verify the neuroprotection of NSP in the non-tPA-induced intracerebral hemorrhage (ICH) mouse model. METHODS: C57BL/6J male mice (n = 198) were involved in this study. ICH models were established with infusion of autologous blood into the brain parenchyma...
November 7, 2017: BMC Neurology
https://www.readbyqxmd.com/read/29061693/alzheimer-s-disease-a-matter-of-blood-brain-barrier-dysfunction
#8
REVIEW
Axel Montagne, Zhen Zhao, Berislav V Zlokovic
The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD...
November 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29054133/effects-of-intrathecal-injection-of-the-conditioned-medium-of-bone-marrow-stromal-cells-on-spinal-cord-injury-of-rats
#9
Kenji Kanekiyo, Tamami Wakabayashi, Norihiko Nakano, Yoshihiro Yamada, Masahiro Tamachi, Yoshihisa Suzuki, Masanori Fukushima, Fukuki Saito, Seiya Abe, Chihiro Tsukagoshi, Chimi Miyamoto, Chizuka Ide
Bone marrow stromal cells (BMSCs) have been studied for the treatment of spinal cord injury (SCI). In previous studies, we showed that the transplantation of BMSCs, even though they disappeared from the host spinal cord within 1-3 weeks after transplantation, improved locomotor behaviors and promoted axonal regeneration. This result led to the hypothesis that BMSCs might release some neurotrophic factors effective for the treatment of SCI. The present study examined this by injecting the conditioned medium (CM) of BMSCs to treat SCI in rats...
October 20, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28987927/blood-brain-barrier-dysfunction-and-recovery-after-ischemic-stroke
#10
REVIEW
Xiaoyan Jiang, Anuska V Andjelkovic, Ling Zhu, Tuo Yang, Michael V L Bennett, Jun Chen, Richard F Keep, Yejie Shi
The blood-brain barrier (BBB) plays a vital role in regulating the trafficking of fluid, solutes and cells at the blood-brain interface and maintaining the homeostatic microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the BBB can be disrupted, followed by the extravasation of blood components into the brain and compromise of normal neuronal function. This article reviews recent advances in our knowledge of the mechanisms underlying BBB dysfunction and recovery after ischemic stroke...
October 5, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28987284/lentivirus-carrying-the-neurod1-gene-promotes-the-conversion-from-glial-cells-into-neurons-in-a-spinal-cord-injury-model
#11
Wenhao Chen, Baoquan Zhang, Shuxia Xu, Ren Lin, Wei Wang
In this study, we aimed to reprogram reactive glial cells into neural stem cells and neurons in vivo, by up-regulating NeuroD1. 60 rats were randomly divided into three groups with equal numbers. All rats received a spinal cord injury. Group A received only normal saline injection. Group B received unloaded lentivirus injection. Group C received NeuroD1 recombinant lentivirus injection. The BBB scores of the animals were documented at 3, 7, 14, 21days after SCI. 5 random rats of each group were removed at those timings after SCI and sacrificed...
October 5, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28966235/ginsenoside-rg1-promotes-the-migration-of-olfactory-ensheathing-cells-via-the-pi3k-akt-pathway-to-repair-rat-spinal-cord-injury
#12
Yin-Yao Tang, Wei-Xiao Guo, Zheng-Feng Lu, Mao-Hua Cheng, Yi-Xin Shen, Ying-Zi Zhang
The aim of this study was to determine the effects of ginsenoside Rg1 on the migration of olfactory ensheathing cells (OECs) in vitro, and its influence on the therapeutic efficacy of OECs transplanted in vivo for the treatment of spinal cord injury (SCI). Primary cultured and purified OECs (prepared from rats) were treated with ginsenoside Rg1. The wound healing test indicated that ginsenoside Rg1 promoted the migration of OECs. Real-time RT-PCR demonstrated that ginsenoside Rg1 upregulated the expression of migration-related factors of OECs, including matrix metalloproteinases-2 (MMP-2), MMP-9, and neural cell adhesion molecule 1 (NCAM1)...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28938612/magnetic-resonance-imaging-tracking-and-assessing-repair-function-of-the-bone-marrow-mesenchymal-stem-cells-transplantation-in-a-rat-model-of-spinal-cord-injury
#13
Hongwu Zhang, Liqin Wang, Shihong Wen, Qingfeng Xiang, Xianhong Xiang, Caixia Xu, Yong Wan, Jingnan Wang, Bin Li, Yiqian Wan, Zhiyun Yang, David Y B Deng
The transplantation of bone marrow mesenchymal stem cells (BMSCs) to repair spinal cord injury (SCI) has become a promising therapy. However, there is still a lack of visual evidence directly implicating the transplanted cells as the source of the improvement of spinal cord function. In this study, BMSCs were labeled with NF-200 promoter and lipase-activated gadolinium-containing nanoparticles (Gd-DTPA-FA). Double labeled BMSCs were implanted into spinal cord transaction injury in rat models in situ, the function recovery was evaluated on 1st, 7th, 14th, 28 th days by MRI, Diffusion Tensor Imaing, CT imaging and post-processing, and histological observations...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901688/poly-glycerol-sebacate-combined-with-chondroitinase-abc-promotes-spinal-cord-repair-in-rats
#14
Qi Pan, Yan Guo, Fanyong Kong
This study was to investigate the feasibility of PGS combined with ChABC for repairing the transection of spinal cords (TSC) in rats. A thoracic 10 (T10) TSC model of rats was employed. The effects of PGS with ChABC on the morphology and histological structure of the spinal cords, Basso, Beattie, Bresnahan (BBB) scores, and the expression of GAP-43 and NF-200 were comparatively studied. The BBB scores indicated that all rats with TSC were paralyzed immediately after surgery and then recovered hind limb movement gradually, but did not fully recover until the end of week 12...
September 13, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28744122/penetration-of-blood-brain-barrier-and-antitumor-activity-and-nerve-repair-in-glioma-by-doxorubicin-loaded-monosialoganglioside-micelles-system
#15
Dan Zou, Wei Wang, Daoxi Lei, Ying Yin, Peng Ren, Jinju Chen, Tieying Yin, Bochu Wang, Guixue Wang, Yazhou Wang
For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28740568/methane-suppresses-microglial-activation-related-to-oxidative-inflammatory-and-apoptotic-injury-during-spinal-cord-injury-in-rats
#16
WeiHeng Wang, Xiaodong Huang, Jian Li, Aijun Sun, Jiangming Yu, Ning Xie, YanHai Xi, Xiaojian Ye
OBJECTIVE: We investigated the hypothesis that methane-rich saline (MS) can be used to repair spinal cord injury (SCI) in a rat model through suppressing microglial activation related to oxidative, inflammatory, and apoptotic injury. METHODS: MS was injected intraperitoneally in rats after SCI. Hematoxylin-eosin (HE) staining, oxidative stress, inflammatory parameters, and cell apoptosis were detected 72 h after SCI to determine the optimal dose. Then, we investigated the protective mechanisms and the long-term effects of MS on SCI...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28738875/effects-of-fty720-on-brain-neurogenic-niches-in-vitro-and-after-kainic-acid-induced-injury
#17
Raffaela Cipriani, Juan Carlos Chara, Alfredo Rodríguez-Antigüedad, Carlos Matute
BACKGROUND: FTY720 (fingolimod, Gilenya™) is an oral, blood-brain barrier (BBB)-passing drug approved as immunomodulatory treatment for relapsing-remitting form of the multiple sclerosis (MS). In addition, FTY720 exerts several effects in the central nervous system (CNS), ranging from neuroprotection to reduction of neuroinflammation. However, the neurogenic and oligodendrogenic potential of FTY720 has been poorly investigated. In this study, we assessed the effect of FTY720 on the production of new neurons and oligodendrocytes from neural stem/precursor cells both in vitro and in vivo...
July 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28710563/an-observational-study-examining-the-effects-of-a-surgically-induced-inflammatory-response-on-the-distribution-of-morphine-and-its-metabolites-into-cerebrospinal-fluid
#18
Yan Wang, Kerry B Goralski, Derek J Roberts, Kathryn Landry, Mark E Issa, Lekha Sleno, Lisa C Julien, Jeremy Wood, Richard I Hall
PURPOSE: Morphine is administered intravenously for pain management in the perioperative period. The effect of the inflammatory response to surgery on morphine distribution across the blood-brain barrier (BBB) in humans was investigated. We hypothesized that a graded surgically induced, systemic inflammatory response alters cerebrospinal fluid (CSF) levels of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a temporary reduction in BBB drug efflux transporter function...
July 14, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28683586/vitronectin-regulates-the-fibrinolytic-system-during-the-repair-of-cerebral-cortex-in-stab-wounded-mice
#19
Kei Hashimoto, Natsumi Ikeda, Mari Nakashima, Hiroko Ikeshima-Kataoka, Yasunori Miyamoto
Vitronectin (VN), one of the serum proteins, is known to be involved in the regulation of blood coagulation, fibrinolysis, and cell migration. It has been proposed that the regulation of fibrinolysis by VN promotes the blood-brain barrier (BBB) recovery from brain injuries such as traumatic injury and subarachnoid hemorrhage. The effects of VN on fibrinolysis in the injured brain remain unclear, however. We examined the effects of VN on the fibrinolytic system in the stab-wounded cerebral cortex of VN-knockout (KO) mice...
November 15, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28670310/sepsis-associated-encephalopathy-the-blood-brain-barrier-and-the-sphingolipid-rheostat
#20
REVIEW
Stephen J Kuperberg, Raj Wadgaonkar
Sepsis is not only a significant cause of mortality worldwide but has particularly devastating effects on the central nervous system of survivors. It is therefore crucial to understand the molecular structure, physiology, and events involved in the pathogenesis of sepsis-associated encephalopathy, so that potential therapeutic advances can be achieved. A key determinant to the development of this type of encephalopathy is morphological and functional modification of the blood-brain barrier (BBB), whose function is to protect the CNS from pathogens and toxic threats...
2017: Frontiers in Immunology
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