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https://www.readbyqxmd.com/read/28182332/challenging-the-great-vascular-wall-can-we-envision-a-simple-yet-comprehensive-therapy-for-stroke
#1
Marta Machado-Pereira, Tiago Santos, Lino Ferreira, Liliana Bernardino, Raquel Ferreira
Stroke is a leading cause of death in adult life, closely behind ischemic heart disease, and causes a significant and abiding socioeconomic burden. However, current therapies are not able to ensure full neurologic and/or sequelae-free recovery to all stroke survivors. We believe treatment efficacy and patient rehabilitation could be enhanced significantly by targeting blood-brain barrier (BBB) deregulation and inflammation-induced barrier loss occurring after stroke. In this pathological context, bone marrow-derived endothelial progenitor cells (EPC) enter the bloodstream towards the lesion site but their insufficient numbers and impaired angiogenic ability compromise neurovascular regeneration...
February 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28144983/human-olfactory-mesenchymal-stromal-cell-transplants-promote-remyelination-and-earlier-improvement-in-gait-co-ordination-after-spinal-cord-injury
#2
Susan L Lindsay, Andrew Toft, Jacob Griffin, Ahmed M M Emraja, Susan Carol Barnett, John S Riddell
Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals. In addition to the typical distribution in the dorsal columns (common to all animals), in transplanted animals only, P0 immunolabelling was consistently detected in white matter lateral and ventral to the injury site...
February 1, 2017: Glia
https://www.readbyqxmd.com/read/28142208/intravenously-transplanted-human-bone-marrow-endothelial-progenitor-cells-engraft-within-brain-capillaries-preserve-mitochondrial-morphology-and-display-pinocytotic-activity-towards-bbb-repair-in-ischemic-stroke-rats
#3
Svitlana Garbuzova-Davis, Edward Haller, Roger Lin, Cesario V Borlongan
Stroke is a life threatening disease with limited therapeutic options. Cell therapy has emerged as an experimental stroke treatment. Blood-brain barrier (BBB) impairment is a key pathological manifestation of ischemic stroke, and barrier repair is an innovative target for neurorestoration in stroke. Here, we evaluated via electron microscopy the ability of transplanted human bone marrow endothelial progenitor cells (hBMEPCs) to repair the BBB in adult Sprague-Dawley rats subjected to transient middle cerebral artery occlusion (tMCAO)...
January 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28137846/endothelial-wnt-%C3%AE-catenin-signaling-reduces-immune-cell-infiltration-in-multiple-sclerosis
#4
Justin E Lengfeld, Sarah E Lutz, Julian R Smith, Claudiu Diaconu, Cameron Scott, Sigal B Kofman, Claire Choi, Craig M Walsh, Cedric S Raine, Ilir Agalliu, Dritan Agalliu
Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28124770/the-effect-of-stereotactic-injections-on-demyelination-and-remyelination-a-study-in-the-cuprizone-model
#5
Laura Salinas Tejedor, Tanja Wostradowski, Stefan Gingele, Thomas Skripuletz, Viktoria Gudi, Martin Stangel
Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination...
January 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28124594/strategies-of-engineering-nanoparticles-for-treating-neurodegenerative-disorders
#6
Khanh Tu Nguyen, Minh Nguyet Pham, Toi Van Vo, Wei Duan, Phuong Ha-Lien Tran, Tran Truong-Dinh Thao
Neurodegenerative disorders (NDs) are typically referred to Alzheimer's disease, Parkinson's diseases, amyotrophic lateral sclerosis and prion disease. These are commonly debilitating and, unfortunately, have few therapeutic options. One of the main difficulties in fighting against NDs is to overcome the shielding of blood-brain barrier (BBB), which greatly limits the penetration of various therapeutic drugs, which sometimes leads to severe side effects. Nanotechnology, by engineering materials of a size scale usually within 1-100 nm, fortunately offers an alternative approach for novel, promising and innovative solutions...
January 25, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28112873/transplantation-of-human-bone-marrow-derived-clonal-mesenchymal-stem-cells-reduces-ffibrotic-sscar-fformation-in-a-rat-spinal-cord-injury-model
#7
Moonhang Kim, Kil Hwan Kim, Sun U Song, Tac Ghee Yi, Seung Hwan Yoon, So Ra Park, Byung Hyune Choi
This study aimed at evaluating the therapeutic effect on tissue repair and scar formation of human bone marrow-derived clonal mesenchymal stem cells (hcMSCs) homogeneously isolated by using a subfractionation culturing method, in comparison with the non-clonal MSCs (hMSCs), in a rat spinal cord injury (SCI) model. The SCI was made using a vascular clip at the T9 level. Cells were transplanted into the lesion site 3 days after injury. A functional test was performed over 4 weeks employing a BBB score. Rats were killed for histological analysis at 3 days, 1 week and 4 weeks after injury...
January 23, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097067/anatomical-mechanism-of-spontaneous-recovery-in-regions-caudal-to-thoracic-spinal-cord-injury-lesions-in-rats
#8
Lu-Sheng Li, Hao Yu, Raynald Raynald, Xiao-Dong Wang, Guang-Hui Dai, Hong-Bin Cheng, Xue-Bin Liu, Yi-Hua An
BACKGROUND: The nerve fibre circuits around a lesion play a major role in the spontaneous recovery process after spinal cord hemisection in rats. The aim of the present study was to answer the following question: in the re-control process, do all spinal cord nerves below the lesion site participate, or do the spinal cord nerves of only one vertebral segment have a role in repair? METHODS: First we made a T7 spinal cord hemisection in 50 rats. Eight weeks later, they were divided into three groups based on distinct second operations at T7: ipsilateral hemisection operation, contralateral hemisection, or transection...
2017: PeerJ
https://www.readbyqxmd.com/read/28088914/diverse-functions-and-mechanisms-of-pericytes-in-ischemic-stroke
#9
Shuai Yang, Huijuan Jin, Yiyi Zhu, Yan Wan, Lingqiang Zhu, Bo Hu
Pericytes are mural cells embedded in the basement membrane of microvessels. Because of such a unique position in the blood-brain barrier (BBB) and neurovascular unit (NVU), they receive, orchestrate and process signals from their neighboring cells to generate diverse neurovascular functions, including regulation of capillary hemodynamics, BBB permeability, clearance of toxic metabolites, angiogenesis, neuroinflammation and stem cell activity. During the different stages of ischemic stroke, pericytes play different roles: 1) On the hyperacute phase of stroke, pericytes constriction and death may be a cause of the no-reflow phenomenon in brain capillaries; 2) During the acute phase, pericytes detach from microvessels and participate in inflammatory-immunological response, resulting in the BBB damage and brain edema...
January 12, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28077367/electroacupuncture-alleviates-the-inflammatory-response-via-effects-on-m1-and-m2-macrophages-after-spinal-cord-injury
#10
Jiagui Zhao, Rongyi Zhang, Likui Wang, Yuanhai Li
BACKGROUND: Macrophages/microglia are important effector cells at the site of spinal cord injury (SCI). M1-type macrophages facilitate innate immunity to remove foreign microbes and wound debris from the injury site. M2-type macrophages exhibit tissue repair properties and attenuate production of pro-inflammatory cytokines. Regulation of the polarisation of M1/M2 macrophages may affect the inflammatory response in SCI and may be related to neurotrophin-3 (NT-3). Electroacupuncture (EA) at GV acupuncture points can be used as an adjuvant therapy for SCI...
January 11, 2017: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/27924726/neurodegenerative-disease-a-perspective-on-cell-based-therapy-in-the-new-era-of-cell-free-nano-therapy
#11
Su M Metcalfe, Sean Bickerton, Tarek Fahmy
Neurodegenerative diseases (NDD) result in irreversible loss of neurons. Dementia develops when disease-induced neuronal loss becomes sufficient to impair both memory and cognitive functioning and, globally, dementia is increasing to epidemic proportions as populations age. In the current era of regenerative medicine intense activity is asking, can loss of endogenous neurons be compensated by replacement with exogenously derived cells that have either direct, or indirect, neurogenic capacity? But, more recently, excitement is growing around an emerging alternative to the cell-based approach - here nanotechnology for targeted delivery of growth factor aims to support and expand resident central nervous system (CNS) stem cells for endogenous repair...
December 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27921243/comparison-of-rnai-ngr-and-nep1-40-in-acting-on-axonal-regeneration-after-spinal-cord-injury-in-rat-models
#12
Jing Xu, Jian He, Huang He, Renjun Peng, Jian Xi
This study was intended to compare the therapeutic efficacies of NEP1-40 and SiNgR199 on treating spinal cord injury (SCI). Nogo-A, growth associated protein 43 (GAP-43), microtubule associated protein 2 (MAP-2), and amyloid βA4 precursor protein (APP) expressions were determined using western blot and quantitative PCR. Neurite outgrowth detected the growth of neurites, and BDA anterograde tracing was used to label the regenerated axonal. Rats' behavior was assessed with Basso, Beattie, and Bresnahan locomotor rating scale (BBB)...
December 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27903223/releasing-of-herpes-simplex-virus-carrying-ngf-in-subarachnoid-space-promotes-the-functional-repair-in-spinal-cord-injured-rats
#13
Zhi-Wei Chen, Hang-Ping Wang, Feng-Mei Yuan, Xiao Zhang, Xiu-Juan Dong, Rui-Shen Xie, Chao Tian, Bing-Shen Li, Zhen-Wu Sun, Long-Hui Zhou, Jian Liu, Tinghua Wang
BACKGROUND: Spinal cord injury is a serious disease which can lead to bad consequence in patients. Gene therapies as an effective strategy, has been developed for the treatment of disease. OBJECTIVE: Here, we explored the effect of NGF release carried by HSV-1 in the injured spinal cord. METHODS: Transgenic recombinant containing NGF was constructed by using clone technology. NGF was firstly constructed into plasimid, then enveloped by HSV-1 vector...
November 20, 2016: Current Gene Therapy
https://www.readbyqxmd.com/read/27897111/aggressive-antioxidant-reductive-stress-impairs-brain-endothelial-cell-angiogenesis-and-blood-brain-barrier-function
#14
Shireen Mentor, David Fisher
Oxidative stress in the brain microvasculature is a common characteristic in models of cerebrovascular disease. Considering the effects of reactive oxygen species activity in vascular-derived insults, it is naturally prudent to hypothesize those interventions inhibiting reactive oxygen species activity, such as antioxidant supplementation, may be beneficial for cerebrovascular disease. Hyper doses of antioxidant supplements, and foods with high antioxidant concentrations, are commonly used as an ongoing remedial and 'over-the-counter' treatments for most seasonal ailments...
November 29, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27863083/promotion-of-neurological-recovery-in-rat-spinal-cord-injury-by-mesenchymal-stem-cells-loaded-on-nerve-guided-collagen-scaffold-through-increasing-alternatively-activated-macrophage-polarization
#15
Zhan Peng, Wei Gao, Bing Yue, Jie Jiang, Yong Gu, Jianwu Dai, Liang Chen, Qin Shi
Mesenchymal stem cells(MSCs)characterized by multi-differentiation potent and immunoregulatory have been used in the treatment of spinal cord injury (SCI), but the direct transplantation may limit its effectiveness due to quick diffusion. In addition, the role of macrophages in healing is being increasingly recognized because of the ability to polarize into pro- and anti-inflammatory phenotypes. In the present study, we developed the nerve-guide collagen scaffold (CS) and rat MSCs. After CS was confirmed to minimize MSCs distribution in vivo by the positron emission tomography (PET) imaging, the repair capacity of combined implantation of CS and MSCs and the effect on classically activated macrophage (M1)/alternatively activated macrophage (M2) polarization was assessed in a hemisected SCI rat model...
November 15, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27837475/pericytes-in-brain-injury-and-repair-after-ischemic-stroke
#16
REVIEW
Wei Cai, Huan Liu, Jingyan Zhao, Lily Y Chen, Jun Chen, Zhengqi Lu, Xiaoming Hu
Pericytes are functional components of the neurovascular unit (NVU). They provide support to other NVU components and maintain normal physiological functions of the blood-brain barrier (BBB). The brain ischemia and reperfusion result in pathological alterations in pericytes. The intimate anatomical and functional interactions between pericytes and other NVU components play pivotal roles in the progression of stroke pathology. In this review, we depict the biology and functions of pericytes in the normal brain and discuss their effects in brain injury and repair after ischemia/reperfusion...
November 12, 2016: Translational Stroke Research
https://www.readbyqxmd.com/read/27789279/conditioned-medium-of-olfactory-ensheathing-cells-promotes-the-functional-recovery-and-axonal-regeneration-after-contusive-spinal-cord-injury
#17
Mengchao Gu, Zhengchao Gao, Xiaohui Li, Lei Guo, Teng Lu, Yuhuan Li, Xijing He
OBJECTIVE: To investigate the effectiveness and the potential role of olfactory ensheathing cell conditioned medium (OEC-M) to treat contusive spinal cord injury (SCI). METHODS: The contusive SCI model was established by NYU weight-drop impactor at T10 segment. Male Sprague-Dawley rats received intraperitoneal injection of control medium (Con-M, n=18), low dose OEC-M (n=18) and high dose OEC-M (n=18). Immunofluorescence was performed to identify the purity of cultured OECs...
January 1, 2017: Brain Research
https://www.readbyqxmd.com/read/27738326/radiosensitizing-effect-of-lapatinib-in-human-epidermal-growth-factor-receptor-2-positive-breast-cancer-cells
#18
Tosol Yu, Bong Jun Cho, Eun Jung Choi, Ji Min Park, Dan Hyo Kim, In Ah Kim
Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer.To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27707627/sobetirome-prodrug-esters-with-enhanced-blood-brain-barrier-permeability
#19
Andrew T Placzek, Skylar J Ferrara, Meredith D Hartley, Hannah S Sanford-Crane, J Matthew Meinig, Thomas S Scanlan
There is currently great interest in developing drugs that stimulate myelin repair for use in demyelinating diseases such as multiple sclerosis. Thyroid hormone plays a key role in stimulating myelination during development and also controls the expression of important genes involved in myelin repair in adults. Because endogenous thyroid hormone in excess lacks a generally useful therapeutic index, it is not used clinically for indications other than hormone replacement; however, selective thyromimetics such as sobetirome offer a therapeutic alternative...
November 15, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27698773/neural-stem-cell-transplantation-combined-with-erythropoietin-for-the-treatment-of-spinal-cord-injury-in-rats
#20
Yan Zhao, Yuan Zuo, Jianming Jiang, Huibo Yan, Xiliang Wang, Hunjun Huo, Yulong Xiao
Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group)...
October 2016: Experimental and Therapeutic Medicine
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