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https://www.readbyqxmd.com/read/27699230/a-cord-blood-monocyte-derived-cell-therapy-product-accelerates-brain-remyelination
#1
Arjun Saha, Susan Buntz, Paula Scotland, Li Xu, Pamela Noeldner, Sachit Patel, Amy Wollish, Aruni Gunaratne, Tracy Gentry, Jesse Troy, Glenn K Matsushima, Joanne Kurtzberg, Andrew E Balber
Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14(+) monocytes. We compared the ability of freshly isolated CB CD14(+) monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγ(null) mice following cuprizone feeding-mediated demyelination...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/26527561/cord-blood-mononuclear-cells-prevent-neuronal-apoptosis-in-response-to-perinatal-asphyxia-in-the-newborn-lamb
#2
James D S Aridas, Courtney A McDonald, Madison C B Paton, Tamara Yawno, Amy E Sutherland, Ilias Nitsos, Yen Pham, Michael Ditchfield, Michael C Fahey, Flora Wong, Atul Malhotra, Margie Castillo-Melendez, Kishore Bhakoo, Euan M Wallace, Graham Jenkin, Suzanne L Miller
Perinatal asphyxia is a significant cause of death or long-term neurodevelopmental impairment. Hypothermia, currently the only effective treatment, leads to modest improvements, but new therapeutic strategies are required. Umbilical cord blood (UCB) mononuclear cells have potent anti-inflammatory properties and may reduce neuropathology. This study examined whether autologous UCB mononuclear cells were neuroprotective when administered to newborn lambs at 12 h after birth asphyxia. At caesarean section, birth asphyxia was induced by clamping the umbilical cord until mean arterial blood pressure decreased to 18-20 mmHg...
March 1, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/26276011/reprint-of-preclinical-characterization-of-duoc-01-a-cell-therapy-product-derived-from-banked-umbilical-cord-blood-for-use-as-an-adjuvant-to-umbilical-cord-blood-transplantation-for-treatment-of-inherited-metabolic-diseases
#3
Joanne Kurtzberg, Susan Buntz, Tracy Gentry, Pamela Noeldner, April Ozamiz, Benjamin Rusche, Robert W Storms, Amy Wollish, David A Wenger, Andrew E Balber
BACKGROUND AIMS: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. METHODS: DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process...
September 2015: Cytotherapy
https://www.readbyqxmd.com/read/25770677/preclinical-characterization-of-duoc-01-a-cell-therapy-product-derived-from-banked-umbilical-cord-blood-for-use-as-an-adjuvant-to-umbilical-cord-blood-transplantation-for-treatment-of-inherited-metabolic-diseases
#4
Joanne Kurtzberg, Susan Buntz, Tracy Gentry, Pamela Noeldner, April Ozamiz, Benjamin Rusche, Robert W Storms, Amy Wollish, David A Wenger, Andrew E Balber
BACKGROUND AIMS: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. METHODS: DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process...
June 2015: Cytotherapy
https://www.readbyqxmd.com/read/25278116/advances-in-the-management-of-multiple-sclerosis-spasticity-multiple-sclerosis-spasticity-nervous-pathways
#5
Diego Centonze
BACKGROUND: Spasticity arises from hyperexcitability of the neural stretch reflex arc secondary to injury of the corticospinal tract. In response to injury, the density of glutamatergic inputs from afferent 1A fibers to motor neurons increases dramatically and adaptive changes occur in the morphology of microglia cells in the spinal cord. SUMMARY: Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS...
2014: European Neurology
https://www.readbyqxmd.com/read/24408112/cb%C3%A2-receptor-deficiency-increases-amyloid-pathology-and-alters-tau-processing-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#6
Jeremy Koppel, Valerie Vingtdeux, Philippe Marambaud, Cristina d'Abramo, Heidy Jimenez, Mark Stauber, Rachel Friedman, Peter Davies
The endocannabinoid CB₂ receptor system has been implicated in the neuropathology of Alzheimer's disease (AD). In order to investigate the impact of the CB₂ receptor system on AD pathology, a colony of mice with a deleted CB₂ receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB₂ receptor-sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2⁻/⁻ (Cnr2(tm1Dgen)/J) mice to produce a colony of J20 CNR2⁺/⁺ and J20 CNR2⁻/⁻ mice...
2013: Molecular Medicine
https://www.readbyqxmd.com/read/23808969/changes-in-cb-1-and-cb-2-receptors-in-the-post-mortem-cerebellum-of-humans-affected-by-spinocerebellar-ataxias
#7
Carmen Rodríguez-Cueto, Cristina Benito, Javier Fernández-Ruiz, Julián Romero, Mariluz Hernández-Gálvez, María Gómez-Ruiz
BACKGROUND AND PURPOSE: Spinocerebellar ataxias (SCAs) are a family of chronic progressive neurodegenerative diseases, clinically and genetically heterogeneous, characterized by loss of balance and motor coordination due to degeneration of the cerebellum and its afferent and efferent connections. Unlike other motor disorders, the possible role of changes in the endocannabinoid system in the pathogenesis of SCAs has not been investigated. EXPERIMENTAL APPROACH: The status of cannabinoid receptor type 1 (CB1 ) and cannabinoid receptor type 2 (CB2 ) receptors in the post-mortem cerebellum of SCA patients and controls was investigated using immunohistochemical procedures...
March 2014: British Journal of Pharmacology
https://www.readbyqxmd.com/read/23463725/attenuation-of-hiv-1-replication-in-macrophages-by-cannabinoid-receptor-2-agonists
#8
Servio H Ramirez, Nancy L Reichenbach, Shongshan Fan, Slava Rom, Steven F Merkel, Xu Wang, Wen-Zhe Ho, Yuri Persidsky
Infiltrating monocytes and macrophages play a crucial role in the progression of HIV-1 infection in the CNS. Previous studies showed that activation of the CB₂ can attenuate inflammatory responses and affect HIV-1 infectivity in T cells and microglia. Here, we report that CB₂ agonists can also act as immunomodulators on HIV-1-infected macrophages. First, our findings indicated the presence of elevated levels of CB₂ expression on monocytes/macrophages in perivascular cuffs of postmortem HIV-1 encephalitic cases...
May 2013: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/23370667/anti-neuroinflammatory-activity-of-a-novel-cannabinoid-derivative-by-inhibiting-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-lipopolysaccharide-induced-bv-2-microglial-cells
#9
Sandeep Vasant More, Ju-Young Park, Byung-Wook Kim, Hemant Kumar, Hyung-Woo Lim, Seong-Mook Kang, Sushruta Koppula, Sung-Hwa Yoon, Dong-Kug Choi
Microglial-mediated neuroinflammation has recently been implicated as one of the important mechanisms responsible for the progression of neurodegenerative diseases. Activated microglia cells produce various neurotoxic factors that are harmful to neurons. Therefore, suppression of the inflammatory response elicited by activated microglia is considered a potential therapeutic target for neurodegenerative diseases. The cannabinoid (CB) system is widespread in the central nervous system and is very crucial for modulating a spectrum of neurophysiological functions such as pain, appetite, and cognition...
2013: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/23238740/cannabinoid-receptor-2-signaling-in-peripheral-immune-cells-modulates-disease-onset-and-severity-in-mouse-models-of-huntington-s-disease
#10
Jill Bouchard, Jennifer Truong, Kristofer Bouchard, Diana Dunkelberger, Sandrine Desrayaud, Saliha Moussaoui, Sarah J Tabrizi, Nephi Stella, Paul J Muchowski
Peripheral immune cells and brain microglia exhibit an activated phenotype in premanifest Huntington's disease (HD) patients that persists chronically and correlates with clinical measures of neurodegeneration. However, whether activation of the immune system contributes to neurodegeneration in HD, or is a consequence thereof, remains unclear. Signaling through cannabinoid receptor 2 (CB(2)) dampens immune activation. Here, we show that the genetic deletion of CB(2) receptors in a slowly progressing HD mouse model accelerates the onset of motor deficits and increases their severity...
December 12, 2012: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/22971837/a-cannabigerol-quinone-alleviates-neuroinflammation-in-a-chronic-model-of-multiple-sclerosis
#11
Aitor G Granja, Francisco Carrillo-Salinas, Alberto Pagani, María Gómez-Cañas, Roberto Negri, Carmen Navarrete, Miriam Mecha, Leyre Mestre, Bend L Fiebich, Irene Cantarero, Marco A Calzado, Maria L Bellido, Javier Fernandez-Ruiz, Giovanni Appendino, Carmen Guaza, Eduardo Muñoz
Phytocannabinoids like ∆(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms. Natural and synthetic cannabinoids also target the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ), an attractive molecular target for the treatment of neuroinflammation. As part of a study on the SAR of phytocannabinoids, we have investigated the effect of the oxidation modification in the resorcinol moiety of cannabigerol (CBG) on CB(1), CB(2) and PPARγ binding affinities, identifying cannabigerol quinone (VCE-003) as a potent anti-inflammatory agent...
December 2012: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/22903455/a-cannabinoid-type-2-receptor-agonist-attenuates-blood-brain-barrier-damage-and-neurodegeneration-in-a-murine-model-of-traumatic-brain-injury
#12
Peter S Amenta, Jack I Jallo, Ronald F Tuma, Melanie B Elliott
After traumatic brain injury (TBI), inflammation participates in both the secondary injury cascades and the repair of the CNS, both of which are influenced by the endocannabinoid system. This study determined the effects of repeated treatment with a cannabinoid type 2 receptor (CB(2) R) agonist on blood-brain barrier integrity, neuronal degeneration, and behavioral outcome in mice with TBI. We also looked for the presence of a prolonged treatment effect on the macrophage/microglial response to injury. C57BL/6 mice underwent controlled cortical impact (CCI) and received repeated treatments with a CB(2) R agonist, 0-1966, or vehicle...
December 2012: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/22895861/small-animal-pet-imaging-of-the-type-1-and-type-2-cannabinoid-receptors-in-a-photothrombotic-stroke-model
#13
Caroline Vandeputte, Cindy Casteels, Tom Struys, Michel Koole, Daisy van Veghel, Nele Evens, Anneleen Gerits, Tom Dresselaers, Ivo Lambrichts, Uwe Himmelreich, Guy Bormans, Koen Van Laere
PURPOSE: Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB(1) and CB(2)) have been suggested. The purpose of this study was to evaluate CB(1) and CB(2) receptor binding over time in vivo in a rat photothrombotic stroke model using PET. METHODS: CB(1) and CB(2) microPET imaging was performed at regular time-points up to 2 weeks after stroke using [(18)F]MK-9470 and [(11)C]NE40...
November 2012: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/22860209/sativex-like-combination-of-phytocannabinoids-is-neuroprotective-in-malonate-lesioned-rats-an-inflammatory-model-of-huntington-s-disease-role-of-cb1-and-cb2-receptors
#14
Sara Valdeolivas, Valentina Satta, Roger G Pertwee, Javier Fernández-Ruiz, Onintza Sagredo
We have investigated whether a 1:1 combination of botanical extracts enriched in either Δ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, is neuroprotective in Huntington's disease (HD), using an experimental model of this disease generated by unilateral lesions of the striatum with the mitochondrial complex II inhibitor malonate. This toxin damages striatal neurons by mechanisms that primarily involve apoptosis and microglial activation...
May 16, 2012: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/22795792/activation-of-the-cb2-receptor-system-reverses-amyloid-induced-memory-deficiency
#15
Jiang Wu, Bihua Bie, Hui Yang, Jijun J Xu, David L Brown, Mohamed Naguib
Cannabinoid type 2 (CB(2)) agonists are neuroprotective and appear to play modulatory roles in neurodegenerative processes in Alzheimer's disease. We have studied the effect of 1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl) carbonyl) piperidine (MDA7)-a novel selective CB(2) agonist that lacks psychoactivity-on ameliorating the neuroinflammatory process, synaptic dysfunction, and cognitive impairment induced by bilateral microinjection of amyloid-β (Aβ)(1-40) fibrils into the hippocampal CA1 area of rats...
March 2013: Neurobiology of Aging
https://www.readbyqxmd.com/read/22791629/a-cell-population-that-strongly-expresses-the-cb1-cannabinoid-receptor-in-the-ependyma-of-the-rat-spinal-cord
#16
Daniel Garcia-Ovejero, Angel Arevalo-Martin, Beatriz Paniagua-Torija, Yolanda Sierra-Palomares, Eduardo Molina-Holgado
The cells surrounding the central canal of the spinal cord are a source of stem/precursor cells that may give rise to neurons, astrocytes, or oligodendrocytes. However, they are a heterogeneous population that remains poorly understood. Here we describe a subpopulation characterized by their strong expression of the CB(1) cannabinoid receptor, oval/round soma, apical nucleus, a variable number of cilia (0, 1, or 2), and the presence of a single short and occasionally ramified basal process. These cells are mainly located in the lateral and dorsal central canal throughout the spinal cord...
January 1, 2013: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/22689411/chemical-probes-for-the-recognition-of-cannabinoid-receptors-in-native-systems
#17
Lidia Martín-Couce, Mar Martín-Fontecha, Oscar Palomares, Leyre Mestre, Arnau Cordomí, Miriam Hernangomez, Sara Palma, Leonardo Pardo, Carmen Guaza, María L López-Rodríguez, Silvia Ortega-Gutiérrez
Receptors made visible: The described biotin-tagged small-molecule probes with excellent affinities for the CB(1) and CB(2) cannabinoid receptors (CB(1)R and CB(2)R) enable direct visualization of these receptors in native cellular systems, including neurons, microglia, and immune cells. This method could overcome some of the limitations of current methodologies and may help to dissect the complexity of the endogenous cannabinoid system.
July 9, 2012: Angewandte Chemie
https://www.readbyqxmd.com/read/22653796/cd200-cd200r1-interaction-contributes-to-neuroprotective-effects-of-anandamide-on-experimentally-induced-inflammation
#18
Miriam Hernangómez, Leyre Mestre, Fernando G Correa, Frida Loría, Miriam Mecha, Paula M Iñigo, Fabian Docagne, Richard O Williams, José Borrell, Carmen Guaza
The endocannabinoid anandamide (AEA) is released by macrophages and microglia on pathological neuroinflammatory conditions such as multiple sclerosis (MS). CD200 is a membrane glycoprotein expressed in neurons that suppresses immune activity via its receptor (CD200R) mainly located in macrophages/microglia. CD200-CD200R interactions contribute to the brain immune privileged status. In this study, we show that AEA protects neurons from microglia-induced neurotoxicity via CD200-CD200R interaction. AEA increases the expression of CD200R1 in LPS/IFN-γ activated microglia through the activation of CB(2) receptors...
September 2012: Glia
https://www.readbyqxmd.com/read/22442754/the-central-role-of-glia-in-pathological-pain-and-the-potential-of-targeting-the-cannabinoid-2-receptor-for-pain-relief
#19
Jenny L Wilkerson, Erin D Milligan
Under normal conditions, acute pain processing consists of well-characterized neuronal signaling events. When dysfunctional pain signaling occurs, pathological pain ensues. Glial activation and their released factors participate in the mediation of pathological pain. The use of cannabinoid compounds for pain relief is currently an area of great interest for both basic scientists and physicians. These compounds, bind mainly either the cannabinoid receptor subtype 1 (CB(1)R) or cannabinoid receptor subtype 2 (CB(2)R) and are able to modulate pain...
2011: ISRN Anesthesiology
https://www.readbyqxmd.com/read/22428664/cannabinoid-cb-2-receptor-attenuates-morphine-induced-inflammatory-responses-in-activated-microglial-cells
#20
Stefania Merighi, Stefania Gessi, Katia Varani, Debora Fazzi, Prisco Mirandola, Pier Andrea Borea
BACKGROUND AND PURPOSE: Among several pharmacological properties, analgesia is the most common feature shared by either opioid or cannabinoid systems. Cannabinoids and opioids are distinct drug classes that have been historically used separately or in combination to treat different pain states. In the present study, we characterized the signal transduction pathways mediated by cannabinoid CB(2) and µ-opioid receptors in quiescent and LPS-stimulated murine microglial cells. EXPERIMENTAL APPROACH: We examined the effects of µ-opioid and CB(2) receptor stimulation on phosphorylation of MAPKs and Akt and on IL-1β, TNF-α, IL-6 and NO production in primary mouse microglial cells...
August 2012: British Journal of Pharmacology
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