Scoring Central Nervous System Inflammation, Demyelination, and Axon Injury in Experimental Autoimmune Encephalomyelitis

被引:7
作者
Ucciferri, Carmen C. [1 ]
Gower, Annette [2 ]
Alvarez-Sanchez, Nuria [1 ,2 ]
Whetstone, Heather [3 ]
Ramaglia, Valeria [1 ]
Gommerman, Jennifer L. [1 ]
Brand-Arzamendi, Koroboshka [2 ]
Schneider, Raphael [2 ,4 ]
Dunn, Shannon E. [1 ,2 ,5 ]
机构
[1] Univ Toronto, Dept Immunol, Toronto, ON, Canada
[2] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada
[3] Hosp Sick Children, Sickkids Res Inst, Toronto, ON, Canada
[4] St Michaels Hosp, BARLO MS Ctr, Toronto, ON, Canada
[5] Womens Coll Hosp, Womens Coll Res Inst, Toronto, ON, Canada
来源
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS | 2024年 / 204期
关键词
SERUM NEUROFILAMENT LIGHT; MULTIPLE-SCLEROSIS; GM-CSF; INDUCTION; PATHOLOGY; OUTCOMES; MODELS; DAMAGE;
D O I
10.3791/65738
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Experimental autoimmune encephalomyelitis (EAE) is a common immune -based model of multiple sclerosis (MS). This disease can be induced in rodents by active immunization with protein components of the myelin sheath and Complete Freund's adjuvant (CFA) or by the transfer of myelin -specific T effector cells from rodents primed with myelin protein/CFA into naive rodents. The severity of EAE is typically scored on a 5 -point clinical scale that measures the degree of ascending paralysis, but this scale is not optimal for assessing the extent of recovery from EAE. For example, clinical scores remain high in some EAE models (e.g., myelin oligodendrocyte glycoprotein [MOG] peptide -induced model of EAE) despite the resolution of inflammation. Thus, it is important to complement clinical scoring with histological scoring of EAE, which also provides a means to study the underlying mechanisms of cellular injury in the central nervous system (CNS). Here, a simple protocol is presented to prepare and stain spinal cord and brain sections from mice and to score inflammation, demyelination, and axonal injury in the spinal cord. The method for scoring leukocyte infiltration in the spinal cord can also be applied to score brain inflammation in EAE. A protocol for measuring soluble neurofilament light (sNF-L) in the serum of mice using a Small Molecule Assay (SIMOA) assay is also described, which provides feedback on the extent of overall CNS injury in live mice.
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页数:25
相关论文
共 35 条
[1]   Neuroprotective Effect of Glatiramer Acetate on Neurofilament Light Chain Leakage and Glutamate Excess in an Animal Model of Multiple Sclerosis [J].
Aharoni, Rina ;
Eilam, Raya ;
Lerner, Shaul ;
Shavit-Stein, Efrat ;
Dori, Amir ;
Chapman, Joab ;
Arnon, Ruth .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (24)
[2]   Motor neuron pathology in experimental autoimmune encephalomyelitis:: studies in THY1-YFP transgenic mice [J].
Bannerman, PG ;
Hahn, A ;
Ramirez, S ;
Morley, M ;
Bönnemann, C ;
Yu, S ;
Zhang, GX ;
Rostami, A ;
Pleasure, D .
BRAIN, 2005, 128 :1877-1886
[3]   Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study [J].
Benkert, Pascal ;
Meier, Stephanie ;
Schaedelin, Sabine ;
Manouchehrinia, Ali ;
Yaldizli, Ozgur ;
Maceski, Aleksandra ;
Oechtering, Johanna ;
Achtnichts, Lutz ;
Conen, David ;
Derfuss, Tobias ;
Lalive, Patrice H. ;
Mueller, Christian ;
Muller, Stefanie ;
Naegelin, Yvonne ;
Oksenberg, Jorge R. ;
Pot, Caroline ;
Salmen, Anke ;
Willemse, Eline ;
Kockum, Ingrid ;
Blennow, Kaj ;
Zetterberg, Henrik ;
Gobbi, Claudio ;
Kappos, Ludwig ;
Wiendl, Heinz ;
Berger, Klaus ;
Sormani, Maria Pia ;
Granziera, Cristina ;
Piehl, Fredrik ;
Leppert, David ;
Kuhle, Jens .
LANCET NEUROLOGY, 2022, 21 (03) :246-257
[4]   Obinutuzumab-Induced B Cell Depletion Reduces Spinal Cord Pathology in a CD20 Double Transgenic Mouse Model of Multiple Sclerosis [J].
Breakell, Thomas ;
Tacke, Sabine ;
Schropp, Verena ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Urich, Eduard ;
Kuerten, Stefanie .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (18) :1-17
[5]   Aged hind-limb clasping experimental autoimmune encephalomyelitis models aspects of the neurodegenerative process seen in multiple sclerosis [J].
Cahill, Lindsay S. ;
Zhang, Monan Angela ;
Ramaglia, Valeria ;
Whetstone, Heather ;
Sabbagh, Melika Pahlevan ;
Yi, Tae Joon ;
Woo, Laura ;
Przybycien, Thomas S. ;
Moshkova, Marina ;
Zhao, Fei Linda ;
Rojas, Olga L. ;
Gomes, Josephine ;
Kuerten, Stefanie ;
Gommerman, Jennifer L. ;
Sled, John G. ;
Dunn, Shannon E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (45) :22710-22720
[6]   Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS) [J].
Constantinescu, Cris S. ;
Farooqi, Nasr ;
O'Brien, Kate ;
Gran, Bruno .
BRITISH JOURNAL OF PHARMACOLOGY, 2011, 164 (04) :1079-1106
[7]   The Cytokine GM-CSF Drives the Inflammatory Signature of CCR2+ Monocytes and Licenses Autoimmunity [J].
Croxford, Andrew L. ;
Lanzinger, Margit ;
Hartmann, Felix J. ;
Schreiner, Bettina ;
Mair, Florian ;
Pelczar, Pawel ;
Clausen, Bjoern E. ;
Jung, Steffen ;
Greter, Melanie ;
Becher, Burkhard .
IMMUNITY, 2015, 43 (03) :502-514
[8]   OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages [J].
D'Souza, Cheryl A. ;
Zhao, Fei Linda ;
Li, Xujian ;
Xu, Yan ;
Dunn, Shannon E. ;
Zhang, Li .
PLOS ONE, 2016, 11 (02)
[9]   Serum Neurofilament Light: A Biomarker of Neuronal Damage in Multiple Sclerosis [J].
Disanto, Giulio ;
Barro, Christian ;
Benkert, Pascal ;
Naegelin, Yvonne ;
Schadelin, Sabine ;
Giardiello, Antonella ;
Zecca, Chiara ;
Blennow, Kaj ;
Zetterberg, Henrik ;
Leppert, David ;
Kappos, Ludwig ;
Gobbi, Claudio ;
Kuhle, Jens .
ANNALS OF NEUROLOGY, 2017, 81 (06) :857-870
[10]   Peroxisome Proliferator-Activated Receptor-δ Deficiency in Microglia Results in Exacerbated Axonal Injury and Tissue Loss in Experimental Autoimmune Encephalomyelitis [J].
Doroshenko, Ellinore R. ;
Drohomyrecky, Paulina C. ;
Gower, Annette ;
Whetstone, Heather ;
Cahill, Lindsay S. ;
Ganguly, Milan ;
Spring, Shoshana ;
Yi, Tae Joon ;
Sled, John G. ;
Dunn, Shannon E. .
FRONTIERS IN IMMUNOLOGY, 2021, 12