Suyog Pol1, Ferdinand Schweser2, Nicola Bertolino1, Marilena Preda1, Michele Sveinsson1, Michelle Sudyn1, Natan Babek1, Robert Zivadinov3. 1. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. 2. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA; Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA. 3. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA; Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address: rzivadinov@bnac.net.
Abstract
BACKGROUND: Leptomeningeal inflammation, as evidenced by leptomeningeal contrast enhancement (LMCE), is associated to cortical pathology in multiple sclerosis. The temporal pattern of LMCE in experimental autoimmune encephalomyelitis (EAE) myelin oligodendrocyte glycoprotein (MOG) is unknown. OBJECTIVE: To investigate LMCE using serial MRI in the EAE model of MS, and its association with clinical disease progression. To characterize the relationship between LMCE and underlying histological correlates. DESIGN: Thirteen C57BL/6J mice, MOG-immunized (35-55 amino acid) and 8 saline injected animals were assessed at pre-induction and at 3, 6, 10, 20, 27, 32, 45 and 63 days post induction (dPI). LMCE scan was obtained using FLAIR-RARE sequence after post-contrast gadolinium administration on 9.4 T scanner. Brain cryo-sections were assessed for measuring cellular density of Iba1 positive macrophage/microglia at 10 dPI and 32 dPI, and for the presence of T, B and macrophage cells in the meningeal layer at 10 dPI and 63 dPI. RESULTS: All EAE-MOG animals showed presence of LMCE and none of the control mice. The peak signal intensity of LMCE was evidenced at 10dPI in the meninges and decreased through 10-63 dPI. The peak of LMCE was associated with a weight loss starting at 1 week PI and with clinical symptoms starting at 2 weeks PI. Histological analysis of the brain tissue showed a higher density of Iba1 positive microglial cells in the EAE-MOG animals, corresponding to the areas of LMCE. Meninges of EAE mice showed higher density of Iba1 stained macrophage cells relative to saline animals. EAE animals also showed the presence of T and B cells in the meninges which were absent in the saline animals. CONCLUSIONS: LMCE peak intensity in the meninges corresponds to the acute inflammatory phase of EAE-MOG disease progression, and is associated with clinical symptoms and higher inflammatory cell density.
BACKGROUND:Leptomeningeal inflammation, as evidenced by leptomeningeal contrast enhancement (LMCE), is associated to cortical pathology in multiple sclerosis. The temporal pattern of LMCE in experimental autoimmune encephalomyelitis (EAE) myelin oligodendrocyte glycoprotein (MOG) is unknown. OBJECTIVE: To investigate LMCE using serial MRI in the EAE model of MS, and its association with clinical disease progression. To characterize the relationship between LMCE and underlying histological correlates. DESIGN: Thirteen C57BL/6J mice, MOG-immunized (35-55 amino acid) and 8 saline injected animals were assessed at pre-induction and at 3, 6, 10, 20, 27, 32, 45 and 63 days post induction (dPI). LMCE scan was obtained using FLAIR-RARE sequence after post-contrast gadolinium administration on 9.4 T scanner. Brain cryo-sections were assessed for measuring cellular density of Iba1 positive macrophage/microglia at 10 dPI and 32 dPI, and for the presence of T, B and macrophage cells in the meningeal layer at 10 dPI and 63 dPI. RESULTS: All EAE-MOG animals showed presence of LMCE and none of the control mice. The peak signal intensity of LMCE was evidenced at 10dPI in the meninges and decreased through 10-63 dPI. The peak of LMCE was associated with a weight loss starting at 1 week PI and with clinical symptoms starting at 2 weeks PI. Histological analysis of the brain tissue showed a higher density of Iba1 positive microglial cells in the EAE-MOG animals, corresponding to the areas of LMCE. Meninges of EAE mice showed higher density of Iba1 stained macrophage cells relative to saline animals. EAE animals also showed the presence of T and B cells in the meninges which were absent in the saline animals. CONCLUSIONS:LMCE peak intensity in the meninges corresponds to the acute inflammatory phase of EAE-MOG disease progression, and is associated with clinical symptoms and higher inflammatory cell density.
Authors: Giancarlo Comi; Amit Bar-Or; Hans Lassmann; Antonio Uccelli; Hans-Peter Hartung; Xavier Montalban; Per Solberg Sørensen; Reinhard Hohlfeld; Stephen L Hauser Journal: Ann Neurol Date: 2020-11-04 Impact factor: 10.422
Authors: Shivashankar Othy; Amit Jairaman; Joseph L Dynes; Tobias X Dong; Cornelia Tune; Andriy V Yeromin; Angel Zavala; Chijioke Akunwafo; Fangyi Chen; Ian Parker; Michael D Cahalan Journal: Proc Natl Acad Sci U S A Date: 2020-07-30 Impact factor: 11.205
Authors: Jason M Millward; Paula Ramos Delgado; Alina Smorodchenko; Laura Boehmert; Joao Periquito; Henning M Reimann; Christian Prinz; Antje Els; Michael Scheel; Judith Bellmann-Strobl; Helmar Waiczies; Jens Wuerfel; Carmen Infante-Duarte; Claudia Chien; Joseph Kuchling; Andreas Pohlmann; Frauke Zipp; Friedemann Paul; Thoralf Niendorf; Sonia Waiczies Journal: JCI Insight Date: 2020-11-05