title: Prominent microglial activation in the early proinflammatory immune response in naturally occurring canine spinal cord injury.
abstract: Better understanding of the pathogenesis of spinal cord injury (SCI) is needed for the development of new therapeutic strategies. Spinal cord injury has been investigated in various rodent models, but extrapolation to humans requires the use of a large animal model that more closely mimics human SCI. Dogs frequently develop spontaneous SCI with features that bear a striking resemblance to the human counterpart. We investigated the temporal course of the immune response during naturally occurring canine SCI and in organotypic canine spinal cord slice cultures that are devoid of peripheral immune cells. By immunohistochemistry, the inflammatory response in subacute canine SCI was largely restricted to resident immune cells as demonstrated by activation of major histocompatibility complex class II-expressing microglia/macrophages. By quantitative polymerase chain reaction, there was parallel upregulation of proinflammatory cytokine gene expression (i.e. of interleukin 6 [IL-6] and IL-8 with a trend toward upregulation of tumor necrosis factor) in acute canine SCI. Expression of neuroprotective cytokines (e.g. IL-10) remained unchanged, and transforming growth factor β upregulation was delayed. In organotypic spinal cord slices, there was similar activation of major histocompatibility complex class II-positive microglia and prolonged upregulation of inflammatory cytokines, indicating that resident rather than infiltrating cells play major roles in the postinjury immune response. Thus, canine SCI represents a bridge between rodent models and human SCI that may be relevant for clinical and preclinical treatment studies.
authors.affiliation: Department of Pathology, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Spitzbarth
authors.forename: Patricia
authors.initials: P
authors.lastname: Bock
authors.forename: Verena
authors.initials: V
authors.lastname: Haist
authors.forename: Veronika Maria
authors.initials: VM
authors.lastname: Stein
authors.forename: Andrea
authors.initials: A
authors.lastname: Tipold
authors.forename: Konstantin
authors.initials: K
authors.lastname: Wewetzer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D036383:Ephrin-A2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology*; D046529:Microscopy, Electron, Transmission; D013116:Spinal Cord / Q000473:pathology* / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000662:veterinary; D018709:Statistics, Nonparametric; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D036383:Ephrin-A2; D015395:Histocompatibility Antigens Class I; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha