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https://www.readbyqxmd.com/read/28614713/acute-lesioning-and-rapid-repair-of-hypothalamic-neurons-outside-the-blood-brain-barrier
#1
Ernie Yulyaningsih, Ivan A Rudenko, Martin Valdearcos, Emma Dahlén, Eirini Vagena, Alvin Chan, Arturo Alvarez-Buylla, Christian Vaisse, Suneil K Koliwad, Allison W Xu
Neurons expressing agouti-related protein (AgRP) are essential for feeding. The majority of these neurons are located outside the blood-brain barrier (BBB), allowing them to directly sense circulating metabolic factors. Here, we show that, in adult mice, AgRP neurons outside the BBB (AgRP(OBBB)) were rapidly ablated by peripheral administration of monosodium glutamate (MSG), whereas AgRP neurons inside the BBB and most proopiomelanocortin (POMC) neurons were spared. MSG treatment induced proliferation of tanycytes, the putative hypothalamic neural progenitor cells, but the newly proliferated tanycytes did not become neurons...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28588362/folic-acid-modulates-matrix-metalloproteinase-2-expression-alleviates-neuropathic-pain-and-improves-functional-recovery-in-spinal-cord-injured-rats
#2
Gurwattan S Miranpuri, Sivan Vadakkadath Meethal, Emmanuel Sampene, Abhishek Chopra, Seah Buttar, Carrie Nacht, Neydis Moreno, Kush Patel, Lisa Liu, Anupama Singh, Chandra K Singh, Nithya Hariharan, Bermans Iskandar, Daniel K Resnick
BACKGROUND: The molecular underpinnings of spinal cord injury (SCI) associated with neuropathic pain (NP) are unknown. Recent studies have demonstrated that matrix metalloproteinases (MMPs) such as MMP2 play a critical role in inducing NP following SCI. Promoter methylation of MMPs is known to suppress their transcription and reduce NP. In this context, it has been shown in rodents that folic acid (FA), an FDA approved dietary supplement and key methyl donor in the central nervous system (CNS), increases axonal regeneration and repair of injured CNS in part via methylation...
May 2017: Annals of Neurosciences
https://www.readbyqxmd.com/read/28524176/lentivirus-mediated-microrna-124-gene-modified-bone-marrow-mesenchymal-stem-cell-transplantation-promotes-the-repair-of-spinal-cord-injury-in-rats
#3
Jia-Lin Song, Wei Zheng, Wei Chen, Yun Qian, Yuan-Ming Ouyang, Cun-Yi Fan
Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28494742/potential-gene-therapy-towards-treating-neurodegenerative-diseases-employing-polymeric-nanosystems
#4
Prachi Bangde, Sonal Atale, Anomitra Dey, Ashish Pandit, Prajakta Dandekar, Ratnesh Jain
Recent integrated approaches involving nanotechnology and gene therapy have accelerated development of efficient drug delivery to the central nervous system (CNS). Neurodegenerative disorders are closely associated with genetic inheritance and mutation. Nanotechnology has allowed effective engineering of various such polymeric structures. Moreover, availability of a wide array of polymeric materials has enabled fabrication of biocompatible and biodegradable delivery vehicles. Our review focuses on the ideal features and properties of polymeric nanoparticles that have enabled successful gene therapy for neurodegenerative disorders, as well as the challenges that are posing difficulties in their practical application...
May 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28462801/platelet-rich-plasma-effective-treatment-for-repairing-of-spinal-cord-injury-in-rat
#5
Reza Salarinia, Hamid Reza Sadeghnia, Daryoush Hamidi Alamdari, Seyed Javad Hoseini, Asghar Mafinezhad, Mahmoud Hoseini
OBJECTIVE: The aim of the present study was to evaluate the effect of PRP on the repair of spinal cord injury in rat model. MATERIAL AND METHODS: Rats were randomly divided into three groups with six rats in each group. Then, spinal cord injury was performed under general anesthesia using "weight dropping" method. Control group included rats receiving normal saline, group two received PRP 1 week after injury; group three received PRP 24 h after injury. The motor function was assessed weekly using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale...
April 24, 2017: Acta Orthopaedica et Traumatologica Turcica
https://www.readbyqxmd.com/read/28428179/adamts13-controls-vascular-remodeling-by-modifying-vwf-reactivity-during-stroke-recovery
#6
Haochen Xu, Yongliang Cao, Xing Yang, Ping Cai, Lijing Kang, Ximin Zhu, Haiyu Luo, Lu Lu, Lixiang Wei, Xiaofei Bai, Yuanbo Zhu, Bing-Qiao Zhao, Wenying Fan
Angiogenic response is essential for ischemic brain repair. However, the mechanisms leading to postischemic neovascularization have not been established, and no therapies have been identified. The VWF-cleaving protease ADAMTS13 is required for endothelial tube formation in vitro However, there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited significantly reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke...
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#7
Maria Karamita, Christopher Barnum, Wiebke Möbius, Malú G Tansey, David E Szymkowski, Hans Lassmann, Lesley Probert
Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are important for remyelination in experimental MS models, but it is unknown whether soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration processes. Here, we investigated the specific contribution of solTNF to demyelination and remyelination in the cuprizone model. Treatment with XPro1595, a selective inhibitor of solTNF that crosses the intact blood-brain barrier (BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss and demyelination, but it permitted profound early remyelination due to improved phagocytosis of myelin debris by CNS macrophages and prevented disease-associated decline in motor performance...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28398301/expression-of-autophagy-in-different-stages-of-neurogenic-bladder-after-spinal-cord-injury-in-rats
#8
F-S Zeng, L Zhang, B-J Cui, L-G Huang, Q Zhang, M Sun, B-L Liu, F Meng, Q Li, D-Q Wang, Q-S Sun
STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the expression of autophagy in different stages of the neurogenic bladder after spinal cord injury (SCI) in rats. SETTING: Second Hospital of Shandong University, Jinan, China. METHODS: A total of 36 Wistar rats were divided into the SCI and control groups. In total, six animals were killed and sampled from each group at 1, 4 and 14 days after surgery of T10-T11 level...
April 11, 2017: Spinal Cord
https://www.readbyqxmd.com/read/28182332/challenging-the-great-vascular-wall-can-we-envision-a-simple-yet-comprehensive-therapy-for-stroke
#9
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
#10
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...
April 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-toward-blood-brain-barrier-repair-in-ischemic-stroke-rats
#11
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)...
May 2017: Stem Cells
https://www.readbyqxmd.com/read/28137846/endothelial-wnt-%C3%AE-catenin-signaling-reduces-immune-cell-infiltration-in-multiple-sclerosis
#12
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...
February 14, 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
#13
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...
April 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28124594/strategies-of-engineering-nanoparticles-for-treating-neurodegenerative-disorders
#14
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
#15
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
#16
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
#17
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
#18
Jiagui Zhao, 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
#19
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...
2017: 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
#20
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
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