title: Impaired blood-brain/spinal cord barrier in ALS patients.
abstract: Vascular pathology, including blood-brain/spinal cord barrier (BBB/BSCB) alterations, has recently been recognized as a key factor possibly aggravating motor neuron damage, identifying a neurovascular disease signature for ALS. However, BBB/BSCB competence in sporadic ALS (SALS) is still undetermined. In this study, BBB/BSCB integrity in postmortem gray and white matter of medulla and spinal cord tissue from SALS patients and controls was investigated. Major findings include (1) endothelial cell damage and pericyte degeneration, (2) severe intra- and extracellular edema, (3) reduced CD31 and CD105 expressions in endothelium, (4) significant accumulation of perivascular collagen IV, and fibrin deposits (5) significantly increased microvascular density in lumbar spinal cord, (6) IgG microvascular leakage, (7) reduced tight junction and adhesion protein expressions. Microvascular barrier abnormalities determined in gray and white matter of the medulla, cervical, and lumbar spinal cord of SALS patients are novel findings. Pervasive barrier damage discovered in ALS may have implications for disease pathogenesis and progression, as well as for uncovering novel therapeutic targets.
authors: Center of Excellence for Aging & Brain Repair, University of South Florida, Morsani College of Medicine, Tampa, FL 33612, USA. sgarbuzo@health.usf.edu
authors: Svitlana
authors: S
authors: Garbuzova-Davis
authors: Diana G
authors: DG
authors: Hernandez-Ontiveros
authors: Maria C O
authors: MC
authors: Rodrigues
authors: Edward
authors: E
authors: Haller
authors: Aric
authors: A
authors: Frisina-Deyo
authors: Santhia
authors: S
authors: Mirtyl
authors: Sebastian
authors: S
authors: Sallot
authors: Samuel
authors: S
authors: Saporta
authors: Cesario V
authors: CV
authors: Borlongan
authors: Paul R
authors: PR
authors: Sanberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008297:Male; D008526:Medulla Oblongata / Q000000981:diagnostic imaging / Q000473:pathology*; D008875:Middle Aged; D013116:Spinal Cord / Q000000981:diagnostic imaging / Q000473:pathology*; D019108:Tight Junctions / Q000473:pathology / Q000648:ultrastructure; D014463:Ultrasonography