title: Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS.
abstract: BACKGROUND
  The blood-brain barrier (BBB), blood-spinal cord barrier (BSCB), and blood-cerebrospinal fluid barrier (BCSFB) control cerebral/spinal cord homeostasis by selective transport of molecules and cells from the systemic compartment. In the spinal cord and brain of both ALS patients and animal models, infiltration of T-cell lymphocytes, monocyte-derived macrophages and dendritic cells, and IgG deposits have been observed that may have a critical role in motor neuron damage. Additionally, increased levels of albumin and IgG have been found in the cerebrospinal fluid in ALS patients. These findings suggest altered barrier permeability in ALS. Recently, we showed disruption of the BBB and BSCB in areas of motor neuron degeneration in the brain and spinal cord in G93A SOD1 mice modeling ALS at both early and late stages of disease using electron microscopy. Examination of capillary ultrastructure revealed endothelial cell degeneration, which, along with astrocyte alteration, compromised the BBB and BSCB. However, the effect of these alterations upon barrier function in ALS is still unclear. The aim of this study was to determine the functional competence of the BSCB in G93A mice at different stages of disease.
  
  
  RESULTS
  Evans Blue (EB) dye was intravenously injected into ALS mice at early or late stage disease. Vascular leakage and the condition of basement membranes, endothelial cells, and astrocytes were investigated in cervical and lumbar spinal cords using immunohistochemistry. Results showed EB leakage in spinal cord microvessels from all G93A mice, indicating dysfunction in endothelia and basement membranes and confirming our previous ultrastructural findings on BSCB disruption. Additionally, downregulation of Glut-1 and CD146 expressions in the endothelial cells of the BSCB were found which may relate to vascular leakage.
  
  
  CONCLUSIONS
  Results suggest that the BSCB is compromised in areas of motor neuron degeneration in ALS mice at both early and late stages of the disease.
authors.affiliation: Center of Excellence for Aging & Brain Repair, College of Medicine, University of South Florida, Tampa, Florida, United States of America. sgarbuzo@health.usf.edu
authors.forename: Svitlana
authors.initials: S
authors.lastname: Garbuzova-Davis
authors.forename: Samuel
authors.initials: S
authors.lastname: Saporta
authors.forename: Edward
authors.initials: E
authors.lastname: Haller
authors.forename: Irina
authors.initials: I
authors.lastname: Kolomey
authors.forename: Steven P
authors.initials: SP
authors.lastname: Bennett
authors.forename: Huntington
authors.initials: H
authors.lastname: Potter
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D000818:Animals; D001769:Blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D051379:Mice; D009046:Motor Neurons / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D005456:Fluorescent Dyes; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1