title: Lesion Expansion in Experimental Demyelination Animal Models and Multiple Sclerosis Lesions.
abstract: Gray matter pathology is an important aspect of multiple sclerosis (MS) pathogenesis and disease progression. In a recent study, we were able to demonstrate that the higher myelin content in the white matter parts of the brain is an important variable in the neuroinflammatory response during demyelinating events. Whether higher white matter myelination contributes to lesion development and progression is not known. Here, we compared lesion size of intra-cortical vs. white matter MS lesions. Furthermore, dynamics of lesion development was compared in the cuprizone and lysophosphatidylcholine models. We provide clear evidence that in the human brain, white matter lesions are significantly increased in size as compared to intra-cortical gray matter lesions. In addition, studies using the cuprizone mouse model revealed that the autonomous progression of white matter lesions is more severe compared to that in the gray matter. Focal demyelination revealed that the application of equal amounts of lysophosphatidylcholine results in more severe demyelination in the white compared to the gray matter. In summary, lesion progression is most intense in myelin-rich white matter regions, irrespective of the initial lesion trigger mechanism. A better understanding of myelin debris-triggered lesion expansion will pave the way for the development of new protective strategies in the future.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Große-Veldmann
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Becker
authors.affiliation: Department of Pathology, VU University Medical Center, 1081 HV, Amsterdam, Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
authors.affiliation: Department of Pathology, VU University Medical Center, 1081 HV, Amsterdam, Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.affiliation: Department of Anatomy II, Ludwig-Maximilians-University of Munich, Anatomie Altbau, III. Stock, Raum A330 Pettenkoferstrasse 11, 80336, Munich, Germany. mkipp@ukaachen.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000139:chemically induced* / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology; D066127:White Matter / Q000473:pathology*
chemical_list: D003471:Cuprizone
keywords: Demyelination; Gray matter; Lesion expansion; Multiple sclerosis; Neurodegeneration; White matter