title: Quantifying blood-spinal cord barrier permeability after peripheral nerve injury in the living mouse.
abstract: BACKGROUND
  Genetic polymorphisms, gender and age all influence the risk of developing chronic neuropathic pain following peripheral nerve injury (PNI). It is known that there are significant inter-strain differences in pain hypersensitivity in strains of mice after PNI. In response to PNI, one of the earliest events is thought to be the disruption of the blood-spinal cord barrier (BSCB). The study of BSCB integrity after PNI may lead to a better understanding of the mechanisms that contribute to chronic pain.
  
  
  RESULTS
  Here we used in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to establish a timecourse for BSCB permeability following PNI, produced by performing a spared nerve injury (SNI). From this longitudinal study, we found that the SNI group had a significant increase in BSCB permeability over time throughout the entire spinal cord. The BSCB opening had a delayed onset and the increase in permeability was transient, returning to control levels just over one day after the surgery. We also examined inter-strain differences in BSCB permeability using five mouse strains (B10, C57BL/6J, CD-1, A/J and BALB/c) that spanned the range of pain hypersensitivity. We found a significant increase in BSCB permeability in the SNI group that was dependent on strain but that did not correlate with the reported strain differences in PNI-induced tactile hypersensitivity. These results were consistent with a previous experiment using Evans Blue dye to independently assess the status of the BSCB permeability.
  
  
  CONCLUSIONS
  DCE-MRI provides a sensitive and non-invasive method to follow BSCB permeability in the same group of mice over time. Examining differences between mouse strains, we demonstrated that there is an important genetically-based control of the PNI-induced increase in BSCB permeability and that the critical genetic determinants of BSCB opening after PNI are distinct from those that determine genetic variability in PNI-induced pain hypersensitivity.
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, Toronto, Ontario, Canada. lcahill@mouseimaging.ca.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Cahill
authors.forename: Christine L
authors.initials: CL
authors.lastname: Laliberté
authors.forename: Xue Jun
authors.initials: XJ
authors.lastname: Liu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bishop
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nieman
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Mogil
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sorge
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Jones
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
authors.forename: R Mark
authors.initials: RM
authors.lastname: Henkelman
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D019786:Gadolinium DTPA; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D059348:Peripheral Nerve Injuries / Q000473:pathology*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors; D014851:Wakefulness
chemical_list: C546469:P2rx7 protein, mouse; D058486:Receptors, Purinergic P2X7; D019786:Gadolinium DTPA