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https://www.readbyqxmd.com/read/28430000/neuroprotective-and-regenerative-roles-of-intranasal-wnt-3a-administration-after-focal-ischemic-stroke-in-mice
#1
Zheng Zachory Wei, James Ya Zhang, Tammi M Taylor, Xiaohuan Gu, Yingying Zhao, Ling Wei
Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28428179/adamts13-controls-vascular-remodeling-by-modifying-vwf-reactivity-during-stroke-recovery
#2
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/28426747/metabolic-analysis-of-radioresistant-medulloblastoma-stem-like-clones-and-potential-therapeutic-targets
#3
Lue Sun, Takashi Moritake, Kazuya Ito, Yoshitaka Matsumoto, Hironobu Yasui, Hidehiko Nakagawa, Aki Hirayama, Osamu Inanami, Koji Tsuboi
Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76...
2017: PloS One
https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#4
Giuseppe Migliara, Martin Mueller, Alessia Piermattei, Chaya Brodie, Michael J Paidas, Eytan R Barnea, Francesco Ria
Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis (MS) is a demyelinating autoimmune disease with few clinical forms and uncertain etiology. Current studies suggest that it is likely caused by infection(s) triggering a systemic immune response resulting in antigen/non-antigen-related autoimmune response in central nervous system (CNS). New therapeutic approaches are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a local and systemic immunity regulatory role...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422748/therapeutic-inhibition-of-soluble-brain-tnf-promotes-remyelination-by-increasing-myelin-phagocytosis-by-microglia
#5
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/28412968/interleukin-1-primes-human-mesenchymal-stem-cells-towards-an-anti-inflammatory-and-pro-trophic-phenotype-in-vitro
#6
Elena Redondo-Castro, Catriona Cunningham, Jonjo Miller, Licia Martuscelli, Sarah Aoulad-Ali, Nancy J Rothwell, Cay M Kielty, Stuart M Allan, Emmanuel Pinteaux
BACKGROUND: Inflammation is a key contributor to central nervous system (CNS) injury such as stroke, and is a major target for therapeutic intervention. Effective treatments for CNS injuries are limited and applicable to only a minority of patients. Stem cell-based therapies are increasingly considered for the treatment of CNS disease, because they can be used as in-situ regulators of inflammation, and improve tissue repair and recovery. One promising option is the use of bone marrow-derived mesenchymal stem cells (MSCs), which can secrete anti-inflammatory and trophic factors, can migrate towards inflamed and injured sites or can be implanted locally...
April 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28409229/sphenoid-dysplasia-in-neurofibromatosis-type-1-a-new-technique-for-repair
#7
Di Rocco Concezio, Samii Amir, Tamburrini Gianpiero, Massimi Luca, Giordano Mario
PURPOSE: Sphenoid bone dysplasia in neurofibromatosis type 1 is characterized by progressive exophthalmos and facial disfiguration secondary to herniation of meningeal and cerebral structures. We describe a technique for reconstruction of the sphenoid defect apt at preventing or correcting the ocular globe dislocation. METHODS: After placement of spinal cerebrospinal fluid drainage to reduce intracranial pressure, the temporal pole is posteriorly dislocated extradurally...
April 13, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28407680/transplantation-of-mesenchymal-stem-cells-reverses-behavioural-deficits-and-impaired-neurogenesis-caused-by-prenatal-exposure-to-valproic-acid
#8
Nikolai Gobshtis, Matanel Tfilin, Marina Wolfson, Vadim E Fraifeld, Gadi Turgeman
Neurodevelopmental impairment can affect lifelong brain functions such as cognitive and social behaviour, and may contribute to aging-related changes of these functions. In the present study, we hypothesized that bone marrow-derived mesenchymal stem cells (MSC) administration may repair neurodevelopmental behavioural deficits by modulating adult hippocampal neurogenesis. Indeed, postnatal intracerebral transplantation of MSC has restored cognitive and social behaviour in mice prenatally exposed to valproic acid (VPA)...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407299/effects-of-ultraviolet-radiation-on-glioma-systematic-review
#9
Savva Pronin, Chan Hee Koh, Mark Hughes
Glioblastoma multiforme is the most aggressive primary brain tumour. Treatment is largely palliative, with current strategies unable to prevent inevitable tumour recurrence. Implantable micro-electromechanical systems are becoming more feasible for the management of several human diseases. These systems may have a role in detecting tumour recurrence and delivering localised therapies. One potential therapeutic tool is ultraviolet (UV) light. This systematic review assesses the effects of UV light on glioma cells...
April 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28406160/morphological-detection-and-functional-assessment-of-regenerated-nerve-after-neural-prosthesis-with-a-pgla-nerve-conduit
#10
Dong Gao, Jun-Jian Jiang, Shi-Hui Gu, Jiu-Zhou Lu, Lei Xu
This study aimed to observe the morphological characteristics of a PGLA [poly(glycolide-co-L-lactide)] nerve conduit and regenerated nerve bundle in the human body using high-frequency ultrasound and examine functional recovery of the regenerated nerve using functional magnetic resonance imaging (fMRI) after neural prosthesis with a PGLA nerve conduit. Thirty-nine patients underwent high-frequency ultrasound, and one patient with superficial radial nerve injury (27-mm defect) underwent fMRI at one, three, and six postoperative months...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28400986/combining-injectable-plasma-scaffold-with-mesenchymal-stem-stromal-cells-for-repairing-infarct-cavity-after-ischemic-stroke
#11
Hongxia Zhang, Fen Sun, Jixian Wang, Luokun Xie, Chenqi Yang, Mengxiong Pan, Bei Shao, Guo-Yuan Yang, Shao-Hua Yang, Qichuan ZhuGe, Kunlin Jin
Stroke survivors are typically left with structural brain damage and associated functional impairment in the chronic phase of injury, for which few therapeutic options exist. We reported previously that transplantation of human embryonic stem cell (hESC)-derived neural stem cells together with Matrigel scaffolding into the brains of rats after focal ischemia reduced infarct volume and improved neurobehavioral performance. Matrigel is a gelatinous protein mixture extracted from mouse sarcoma cells, thus would not be approved for use as a scaffold clinically...
April 2017: Aging and Disease
https://www.readbyqxmd.com/read/28399863/vectorized-nanodelivery-systems-for-ischemic-stroke-a-concept-and-a-need
#12
REVIEW
Andrés Da Silva-Candal, Bárbara Argibay, Ramón Iglesias-Rey, Zulema Vargas, Alba Vieites-Prado, Esteban López-Arias, Emilio Rodríguez-Castro, Iria López-Dequidt, Manuel Rodríguez-Yáñez, Yolanda Piñeiro, Tomás Sobrino, Francisco Campos, José Rivas, José Castillo
Neurological diseases of diverse aetiologies have significant effects on the quality of life of patients. The limited self-repairing capacity of the brain is considered to be the origin of the irreversible and progressive nature of many neurological diseases. Therefore, neuroprotection is an important goal shared by many clinical neurologists and neuroscientists. In this review, we discuss the main obstacles that have prevented the implementation of experimental neuroprotective strategies in humans and propose alternative avenues for the use of neuroprotection as a feasible therapeutic approach...
April 11, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28396177/consistent-induction-of-chronic-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice-for-the-longitudinal-study-of-pathology-and-repair
#13
Jonathan P C Hasselmann, Hawra Karim, Anna J Khalaj, Subir Ghosh, Seema K Tiwari-Woodruff
BACKGROUND: While many groups use experimental autoimmune encephalomyelitis (EAE) as a model to uncover therapeutic targets and understand the pathology underlying multiple sclerosis (MS), EAE protocol variability introduces discrepancies in central nervous system (CNS) pathogenesis and clinical disease, limiting the comparability between studies and slowing much-needed translational research. OPTIMIZED METHOD: Here we describe a detailed, reliable protocol for chronic EAE induction in C57BL/6 mice utilizing two injections of myelin oligodendrocyte glycoprotein (35-55) peptide mixed with Complete Freund's Adjuvant and paired with pertussis toxin...
April 7, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28392287/blocked-delayed-or-obstructed-what-causes-poor-white-matter-development-in-intrauterine-growth-restricted-infants
#14
REVIEW
Mary Tolcos, Steven Petratos, Jonathan J Hirst, Flora Wong, Sarah J Spencer, Aminath Azhan, Ben Emery, David W Walker
Poor white matter development in intrauterine growth restricted (IUGR) babies remains a major, untreated problem in neonatology. New therapies, guided by an understanding of the mechanisms that underlie normal and abnormal oligodendrocyte development and myelin formation, are required. Much of our knowledge of the mechanisms that underlie impaired myelination come from studies in adult demyelinating disease, preterm brain injury, or experimental models of hypoxia-ischemia. However relatively less is known for IUGR which is surprising because IUGR is a leading cause of perinatal mortality and morbidity, second only to premature birth...
April 6, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28391011/administration-of-sonic-hedgehog-protein-induces-angiogenesis-and-has-therapeutic-effects-after-stroke-in-rats
#15
Sheng-Cai Chen, Ming Huang, Quan-Wei He, Yan Zhang, Elvis Nana Opoku, Hang Yang, Hui-Juan Jin, Yuan-Peng Xia, Bo Hu
The Sonic hedgehog (Shh) signaling pathway is recapitulated in response to ischemic injury. Here, we investigated the clinical implications of Shh protein in the ischemic stroke and explored the underlying mechanism. Intracerebroventricular injection of Shh, Cyclopamine, or anti-vascular endothelial growth factor (VEGF) was performed immediately after permanent middle cerebral artery occlusion (pMCAO) surgery and lasted for 7days (d). Phosphate-buffered saline (PBS) was used as control. Neurological deficits and infarct volume were examined 7d after pMCAO...
April 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28390712/safe-intrathecal-fluorescein-use-for-identification-of-cerebrospinal-fluid-leaks-case-report-and-perioperative-algorithm-description
#16
M Á Rodríguez-Navarro, C Díaz-Alejo, M L Padilla-Del Rey, A B Alcaraz, P González-Pérez, M Benítez
Intrathecal injection of fluorescein is a method for repairing cerebrospinal fluid fistulas. The most frequent surgical procedure is endonasal endoscopy and the purpose of injecting this dye is to locate the fistula. The anaesthesiologists usually perform the puncture, therefore it is necessary to review this method and to specify some anaesthetic considerations such as correct dosing, safe management protocols and medical-legal aspects. In this case-report we describe the pre, intra and postoperative protocol of action implemented in our department that basically consists of: obtaining a specific consent, prior neurological/ophthalmologic assessment to rule out hypertension and brain damage, use of corticosteroids and previous antihistamines, choosing the correct dose and concentration of intrathecal sodium fluorescein (maximum 1ml at a concentration of 5% diluted in 9ml of cerebrospinal fluid) and close intra and postoperative monitoring...
April 5, 2017: Revista Española de Anestesiología y Reanimación
https://www.readbyqxmd.com/read/28390198/long-term-kinetics-of-immunologic-components-and-neurological-deficits-in-rats-following-repetitive-mild-traumatic-brain-injury
#17
Ruojing Bai, Huabin Gao, Zhaoli Han, Xintong Ge, Shan Huang, Fanglian Chen, Ping Lei
BACKGROUND Despite growing awareness of repetitive mild traumatic brain injury (rmTBI), understanding of the involvement of long-term kinetics of immunologic components in the central and peripheral immune system took part remains incomplete. The present study aimed to provide a quantitative assay for certain immune system parameters in rmTBI rats. MATERIAL AND METHODS Neurological functions were assessed by modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM), immunologic components from brain and peripheral blood were analyzed by flow cytometry (FCM), and concentrations of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were measure by enzyme-linked immunosorbent assay (ELISA)...
April 8, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28386216/calpastatin-overexpression-preserves-cognitive-function-following-seizures-while-maintaining-post-injury-neurogenesis
#18
Vanessa M Machado, Ana Sofia Lourenço, Cláudia Florindo, Raquel Fernandes, Caetana M Carvalho, Inês M Araújo
In the adult mammalian brain, new neurons continue to be produced throughout life in two main regions in the brain, the subgranular zone (SGZ) in the hippocampus and the subventricular zone in the walls of the lateral ventricles. Neural stem cells (NSCs) proliferate in these niches, and migrate as neuroblasts, to further differentiate in locations where new neurons are needed, either in normal or pathological conditions. However, the endogenous attempt of brain repair is not very efficient. Calpains are proteases known to be involved in neuronal damage and in cell proliferation, migration and differentiation of several cell types, though their effects on neurogenesis are not well known...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28385597/ester-to-amide-rearrangement-of-ethanolamine-derived-prodrugs-of-sobetirome-with-increased-blood-brain-barrier-penetration
#19
Skylar J Ferrara, J Matthew Meinig, Andrew T Placzek, Tapasree Banerji, Peter McTigue, Meredith D Hartley, Hannah S Sanford-Crane, Tania Banerji, Dennis Bourdette, Thomas S Scanlan
Current therapeutic options for treating demyelinating disorders such as multiple sclerosis (MS) do not stimulate myelin repair, thus creating a clinical need for therapeutic agents that address axonal remyelination. Thyroid hormone is known to play an important role in promoting developmental myelination and repair, and CNS permeable thyromimetic agents could offer an increased therapeutic index compared to endogenous thyroid hormone. Sobetirome is a clinical stage thyromimetic that has been shown to have promising activity in preclinical models related to MS and X-linked adrenoleukodystrophy (X-ALD), a genetic disease that involves demyelination...
May 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28383788/replication-stress-dna-damage-signalling-and-cytomegalovirus-infection-in-human-medulloblastomas
#20
Jiri Bartek, Olesja Fornara, Joanna Maria Merchut-Maya, Apolinar Maya-Mendoza, Afshar Rahbar, Giuseppe Stragliotto, Helle Broholm, Mikael Svensson, Astrid Sehested, Cecilia Söderberg Naucler, Jiri Bartek, Jirina Bartkova
Medulloblastomas are the most common, and often fatal, paediatric brain tumours that feature high genomic instability, frequent infection by human cytomegalovirus (HCMV) and resistance to radiation and chemotherapy. The causes of the pronounced chromosomal instability and its potential links with HCMV infection and/or resistance to genotoxic therapies remain largely unknown. To address these issues, here we have combined immunohistochemical analysis of a series of 25 paediatric medulloblastomas, complemented by medulloblastoma cell culture models including experimental HCMV infection...
April 6, 2017: Molecular Oncology
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