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https://www.readbyqxmd.com/read/28535416/the-role-of-timing-in-the-treatment-of-spinal-cord-injury
#1
REVIEW
Amene Saghazadeh, Nima Rezaei
Regeneration failure after primary spinal cord injury (SCI) leads to diverse clinical complications in a severity- and level of SCI-dependent manner. The cost of treating both of them (initial regeneration failure and following complications) would be prohibitive, particularly in less developed nations. The well-recognized circumstances arose from primary SCI include excitotoxicity and inflammation. SCI increases concentrations of extracellular amino acids (EAAs) in the severity-dependent manner and the maximum level of EAAs at the injury site will be reduced by distance from the injury site...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28529876/pathology-of-callosal-damage-in-als-an-ex-vivo-7%C3%A2-t-diffusion-tensor-mri-study
#2
Agustin M Cardenas, Joelle E Sarlls, Justin Y Kwan, Devin Bageac, Zachary S Gala, Laura E Danielian, Abhik Ray-Chaudhury, Hao-Wei Wang, Karla L Miller, Sean Foxley, Saad Jbabdi, Robert C Welsh, Mary Kay Floeter
OBJECTIVES: The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. METHODS: Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28504050/how-long-is-sufficient-for-optimal-neuroprotection-with-cerebral-cooling-after-ischemia-in-fetal-sheep
#3
Joanne O Davidson, Vittoria Draghi, Sean Whitham, Simerdeep K Dhillon, Guido Wassink, Laura Bennet, Alistair J Gunn
The optimal duration of mild "therapeutic" hypothermia for neonates with hypoxic-ischemic encephalopathy is surprisingly unclear. This study assessed the relative efficacy of cooling for 48 h versus 72 h. Fetal sheep (0.85 gestation) received sham ischemia (n = 9) or 30 min global cerebral ischemia followed by normothermia (n = 8) or delayed hypothermia from 3 h to 48 h (n = 8) or 72 h (n = 8). Ischemia was associated with profound loss of electroencephalogram (EEG) power, neurons in the cortex and hippocampus, and oligodendrocytes and myelin basic protein expression in the white matter, with increased Iba-1-positive microglia and proliferation...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28503634/an-acute-mouse-spinal-cord-slice-preparation-for-studying-glial-activation-ex-vivo
#4
Juan Mauricio Garré, Guang Yang, Feliksas F Bukauskas, Michael V L Bennett
Pathological conditions such as amyotrophic lateral sclerosis, spinal cord injury and chronic pain are characterized by activation of astrocytes and microglia in spinal cord and have been modeled in rodents. In vivo imaging at cellular level in these animal models is limited due to the spinal cord's highly myelinated funiculi. The preparation of acute slices may offer an alternative and valuable strategy to collect structural and functional information in vitro from dorsal, lateral and ventral regions of spinal cord...
January 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28498493/involvement-of-microglia-in-early-axoglial-alterations-of-the-optic-nerve-induced-by-experimental-glaucoma
#5
Melina P Bordone, María F González Fleitas, Laura A Pasquini, Alejandra Bosco, Pablo H Sande, Ruth E Rosenstein, Damián Dorfman
Glaucoma is a leading cause of blindness, characterized by retinal ganglion cell (RGC) loss and optic nerve (ON) damage. Cumulative evidence suggests glial cell involvement in the degeneration of the ON and RGCs. We analyzed the contribution of microglial reactivity to early axoglial alterations of the ON in an induced model of ocular hypertension. For this purpose, vehicle or chondroitin sulfate (CS) were weekly injected into the eye anterior chamber from Wistar rats for different intervals. The amount of Brn3a(+) RGC significantly decreased in CS-injected eyes for 10 and 15 (but not 6) weeks...
May 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28478826/novel-aspects-of-defensins-involvement-in-virus-induced-autoimmunity-in-the-central-nervous-system
#6
Evangelos I Kazakos, Jannis Kountouras, Stergios A Polyzos, Georgia Deretzi
Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28466255/formyl-peptide-receptor-1-mediated-glial-cell-activation-in-a-mouse-model-of-cuprizone-induced-demyelination
#7
Kai Bihler, Eugenia Kress, Stefan Esser, Stella Nyamoya, Simone C Tauber, Tim Clarner, Matthias B Stope, Thomas Pufe, Lars-Ove Brandenburg
Multiple sclerosis (MS) is a chronic degenerative disease of the central nervous system that is characterized by myelin abnormalities, oligodendrocyte pathology, and concomitant glia activation. Unclear are the factors triggering gliosis and demyelination. New findings suggest an important role of the innate immune response in the initiation and progression of active demyelinating lesions. The innate immune response is induced by pathogen-associated or danger-associated molecular patterns, which are identified by pattern recognition receptors (PRRs), including the G-protein coupled with formyl peptide receptors (FPRs)...
May 2, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28457906/widespread-cortical-demyelination-of-both-hemispheres-can-be-induced-by-injection-of-pro-inflammatory-cytokines-via-an-implanted-catheter-in-the-cortex-of-mog-immunized-rats
#8
Muammer Üçal, Michaela Tanja Haindl, Milena Z Adzemovic, Johannes Strasser, Lisa Theisl, Manuel Zeitelhofer, Klaus Kraitsy, Stefan Ropele, Ute Schäfer, Franz Fazekas, Sonja Hochmeister
Cortical demyelination is a common finding in patients with chronic multiple sclerosis (MS) and contributes to disease progression and overall disability. The exact pathomechanism that leads to cortical lesions is not clear. Research is limited by the fact that standard animal models of multiple sclerosis do not commonly affect the cortex, or if they do in some variants, the cortical demyelination is rather sparse and already remyelinated within a few days. In an attempt to overcome these limitations we implanted a tissue-compatible catheter into the cortex of Dark Agouti rats...
April 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28452087/cytotoxic-cd8-t-cells-ablation-enhances-the-capacity-of-regulatory-t-cells-to-delay-viral-elimination-in-theiler-s-murine-encephalomyelitis
#9
Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Ann-Kathrin Uhde, René Teich, Stephan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke
Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ('Treg-expansion'), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ('CD8-depletion') or (iii) with a combination of Treg-expansion and CD8-depletion ('combined treatment') prior to infection...
April 27, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28445714/the-toll-like-receptor-2-agonist-pam3csk4-is-neuroprotective-after-spinal-cord-injury
#10
Nicole S Stivers, Nicolas Pelisch, Ben C Orem, Joshua Williams, Jacqueline M Nally, David P Stirling
Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28442549/neuraminidases-3-and-4-regulate-neuronal-function-by-catabolizing-brain-gangliosides
#11
Xuefang Pan, Camila De Britto Pará De Aragão, Juan P Velasco-Martin, David A Priestman, Harry Y Wu, Kohta Takahashi, Kazunori Yamaguchi, Luisella Sturiale, Domenico Garozzo, Frances M Platt, Nathalie Lamarche-Vane, Carlos R Morales, Taeko Miyagi, Alexey V Pshezhetsky
Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#12
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
#13
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/28421147/electrophysiological-morphological-and-ultrastructural-features-of-the-injured-spinal-cord-tissue-after-transplantation-of-human-umbilical-cord-blood-mononuclear-cells-genetically-modified-with-the-vegf-and-gdnf-genes
#14
Y O Mukhamedshina, Z E Gilazieva, S S Arkhipova, L R Galieva, E E Garanina, A A Shulman, G G Yafarova, Y A Chelyshev, N V Shamsutdinova, A A Rizvanov
In this study, we examined the efficacy of human umbilical cord blood mononuclear cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using adenoviral vectors, on posttraumatic regeneration after transplantation into the site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by transplantation of nontransduced hUCB-MCs, we observed an improvement in H (latency period, LP) and M(Amax) waves, compared to the group without therapy after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M wave and LP of both the M and H waves...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28412141/toll-like-receptor-4-activation-can-be-either-detrimental-or-beneficial-following-mild-repetitive-traumatic-brain-injury-depending-on-timing-of-activation
#15
Frances Corrigan, Alina Arulsamy, Lyndsey E Collins-Praino, Joshua L Holmes, Robert Vink
A history of repeated concussion has been linked to the later development of neurodegeneration, which is associated with the accumulation of hyperphosphorylated tau and the development of behavioral deficits. However, the role that exogenous factors, such as immune activation, may play in the development of neurodegeneration following repeated mild traumatic brain injury (rmTBI) has not yet been explored. To investigate, male Sprague-Dawley rats were administered three mTBIs 5 days apart using the diffuse impact-acceleration model to generate ∼100G...
April 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28409447/isolation-of-peroxisomes-from-mouse-brain-using-a-continuous-nycodenz-gradient-a-comparison-to-the-isolation-of-liver-and-kidney-peroxisomes
#16
Miriam J Schönenberger, Werner J Kovacs
In the central nervous system (CNS) peroxisomes are present in all cell types, namely neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells. Brain peroxisomes are smaller in size compared to peroxisomes from other tissues and are therefore referred to as microperoxisomes. We have established a purification procedure to isolate highly purified peroxisomes from the central nervous system that are well separated from the endoplasmic reticulum and mitochondria and are free of myelin contamination...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28408633/heterogeneity-of-cortical-lesion-susceptibility-mapping-in-multiple-sclerosis
#17
M Castellaro, R Magliozzi, A Palombit, M Pitteri, E Silvestri, V Camera, S Montemezzi, F B Pizzini, A Bertoldo, R Reynolds, S Monaco, M Calabrese
BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been used to characterize iron and myelin content in the deep gray matter of patients with multiple sclerosis. Our aim was to characterize the susceptibility mapping of cortical lesions in patients with MS and compare it with neuropathologic observations. MATERIALS AND METHODS: The pattern of microglial activation was studied in postmortem brain tissues from 16 patients with secondary-progressive MS and 5 age-matched controls...
April 13, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28392360/matrine-promotes-nt3-expression-in-cns-cells-in-experimental-autoimmune-encephalomyelitis
#18
Ming-Liang Zhang, Xiao-Jian Zhang, Jian Kang, Hui-Jun Zhang, Xiao-Long Chen, Nan Liu, Shu-Qing Liu, Wen-Di Ma, Guang-Xian Zhang, Lin Zhu
Neurotrophin 3 (NT3) is a potent neurotrophic factor for promoting remyelination and recovery of neuronal function; upregulation of its expression in the central nervous system (CNS) is thus of major therapeutic importance for neurological deficits. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flavescent, has been recently reported to effectively ameliorate clinical signs in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by secreting antiinflammatory cytokines...
April 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28357182/expression-of-gpr17-a-regulator-of-oligodendrocyte-differentiation-and-maturation-in-nasu-hakola-disease-brains
#19
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Youhei Tosaki, Kenji Sakai, Tusyoshi Ishida, Yuko Saito
The G protein-coupled receptor 17 (GPR17), a Gi-coupled GPCR, acts as an intrinsic timer of oligodendrocyte differentiation and myelination. The expression of GPR17 is upregulated during differentiation of oligodendrocyte precursor cells (OPCs) into premyelinating oligodendrocytes (preoligodendrocytes), whereas it is markedly downregulated during terminal maturation of myelinating oligodendrocytes. Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2...
February 2017: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/28340598/myelin-specific-multiple-sclerosis-antibodies-cause-complement-dependent-oligodendrocyte-loss-and-demyelination
#20
Yiting Liu, Katherine S Given, Danielle E Harlow, Adeline M Matschulat, Wendy B Macklin, Jeffrey L Bennett, Gregory P Owens
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF. Among these were a subset of myelin-specific MS rAbs. We examined their immunoreactivity to mouse organotypic cerebellar slices by live binding and evaluated tissue injury in the presence and absence of human complement...
March 24, 2017: Acta Neuropathologica Communications
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