title: Demyelination, inflammation, and neurodegeneration in multiple sclerosis deep gray matter.
abstract: Gray matter (GM) lesions are recognized as important components of the pathology of multiple sclerosis (MS), and involvement of the deep gray matter (DGM) is suggested by magnetic resonance imaging. The aims of this study were to determine the frequency and distribution of lesions and characterize the inflammatory and neurodegenerative changes in DGM of MS patients. Histochemistry, immunohistochemistry, and morphometry were performed on whole coronal sections of 14 MS and 12 control (6 normal, 6 from amyotrophic lateral sclerosis patients) brains. Demyelinating lesions were frequent in MS DGM; most often in the thalamus and caudate, but they were also seen in the putamen, pallidum, claustrum, amygdala, hypothalamus, and substantia nigra. Most DGM lesions involved both GM and white matter. Inflammation in active DGM lesions was similar to that in lesions only in white matter but was less intense, and there was a preponderance of activated microglia, scarce myelin-laden macrophages, and a lesser extent of axonal damage. Neuronal loss was observed both in DGM lesions and nondemyelinated DGM with neuron atrophy in nondemyelinated DGM. In conclusion, demyelination and neurodegenerative changes are common in MS DGM and may contribute to clinical impairment. Inflammation in DGM lesions is intermediate between the destructive inflammation of white matter lesions and the minimal inflammation of cortical lesions. We hypothesize that alterations of glutamate reuptake mechanisms may contribute to these differences.
authors.affiliation: Department of Neuroscience, University of Turin, Turin, Italy. vercellino@libero.it
authors.forename: Marco
authors.initials: M
authors.lastname: Vercellino
authors.forename: Silvia
authors.initials: S
authors.lastname: Masera
authors.forename: Marcella
authors.initials: M
authors.lastname: Lorenzatti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Condello
authors.forename: Aristide
authors.initials: A
authors.lastname: Merola
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mattioda
authors.forename: Antonella
authors.initials: A
authors.lastname: Tribolo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Capello
authors.forename: Giovanni Luigi
authors.initials: GL
authors.lastname: Mancardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Mutani
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Giordana
authors.forename: Paola
authors.initials: P
authors.lastname: Cavalla
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D003711:Demyelinating Diseases / Q000209:etiology* / Q000473:pathology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D013194:Staining and Labeling
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D005340:Fibrinogen