title: Ultrastructure of blood-brain barrier and blood-spinal cord barrier in SOD1 mice modeling ALS.
abstract: The purpose of this study was to determine the ultrastructure of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) in G93A SOD1 mice modeling ALS at different stages of disease. Electron microscope examination of brainstem, cervical and lumbar spinal cords was performed in ALS mice at early and late stages of disease. Our results show disorganized mitochondrial cristae and degenerating mitochondria in endothelial cells and neuropil, swollen astrocyte foot processes, swollen and degenerating capillary endothelial cells, astrocytes and motor neurons and extensive extracellular edema. In spite of progressive extracellular edema in neural tissue, capillary endothelial cell tight junctions appeared to remain intact in early and late symptomatic animals. Results show that disruption of BBB and BSCB was evident in areas of motor neuron degeneration in G93A mice at both early and late stages of disease. Capillary rupture was observed in brainstem in early symptomatic G93A mice. Capillary ultrastructure revealed that endothelial cell membrane and/or basement membrane damage occurred, followed by vascular leakage.
authors.affiliation: Center of Excellence for Aging & Brain Repair, University of South Florida, College of Medicine, Tampa, FL 33612, USA. sgarbuzo@health.usf.edu
authors.forename: Svitlana
authors.initials: S
authors.lastname: Garbuzova-Davis
authors.forename: Edward
authors.initials: E
authors.lastname: Haller
authors.forename: Samuel
authors.initials: S
authors.lastname: Saporta
authors.forename: Irina
authors.initials: I
authors.lastname: Kolomey
authors.forename: Santo V
authors.initials: SV
authors.lastname: Nicosia
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000648:ultrastructure; D001485:Basement Membrane / Q000473:pathology / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000648:ultrastructure; D001929:Brain Edema / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D002196:Capillaries / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology* / Q000648:ultrastructure; D005110:Extracellular Space / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D009046:Motor Neurons / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D019108:Tight Junctions / Q000473:pathology / Q000648:ultrastructure
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1