title: Defining peripheral nervous system dysfunction in the SOD-1G93A transgenic rat model of amyotrophic lateral sclerosis.
abstract: Growing evidence indicates that alterations within the peripheral nervous system (PNS) are involved at an early stage in the amyotrophic lateral sclerosis (ALS) pathogenetic cascade. In this study, magnetic resonance imaging (MRI), neurophysiologic analyses, and histologic analyses were used to monitor the extent of PNS damage in the hSOD-1 ALS rat model. The imaging signature of the disease was defined using in vivo MRI of the sciatic nerve. Initial abnormalities were detected in the nerves by an increase in T2 relaxation time before the onset of clinical disease; diffusion MRI showed a progressive increase in mean and radial diffusivity and reduction of fractional anisotropy at advanced stages of disease. Histologic analysis demonstrated early impairment of the blood-nerve barrier followed by acute axonal degeneration associated with endoneurial edema and macrophage response in motor nerve compartments. Progressive axonal degeneration and motor nerve fiber loss correlated with MRI and neurophysiologic changes. These functional and morphologic investigations of the PNS might be applied in following disease progression in preclinical therapeutic studies. This study establishes the PNS signature in this rat ALS model (shedding new light into pathogenesis) and provides a rationale for translating into future systematic MRI studies of PNS involvement in patients with ALS.
authors.affiliation: From the Neuropathology Unit, Institute of Experimental Neurology (NR, LC, TD, GD, FC, GC, AQ) and Division of Neuroscience (NR, LC, DU, FB, FC, PP, UDC, GC, AQ), IRCCS San Raffaele Scientific Institute; Laboratory of Molecular Neurobiology, Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri (MP, GS, CB); Department of Neurorehabilitation Sciences, Casa Cura Policlinico (MC); and Vita e Salute San Raffaele University (GC), Milan, Italy.
authors.forename: Nilo
authors.initials: N
authors.lastname: Riva
authors.forename: Linda
authors.initials: L
authors.lastname: Chaabane
authors.forename: Marco
authors.initials: M
authors.lastname: Peviani
authors.forename: Daniela
authors.initials: D
authors.lastname: Ungaro
authors.forename: Teuta
authors.initials: T
authors.lastname: Domi
authors.forename: Giorgia
authors.initials: G
authors.lastname: Dina
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchi
authors.forename: Giorgia
authors.initials: G
authors.lastname: Spano
authors.forename: Federica
authors.initials: F
authors.lastname: Cerri
authors.forename: Paola
authors.initials: P
authors.lastname: Podini
authors.forename: Massimo
authors.initials: M
authors.lastname: Corbo
authors.forename: Ubaldo Del
authors.initials: UD
authors.lastname: Carro
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Caterina
authors.initials: C
authors.lastname: Bendotti
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001369:Axons / Q000473:pathology; D055724:Electrophysiological Phenomena / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012584:Sciatic Nerve / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1