Cerebrospinal fluid inflammatory cytokines and chemokines in naturally occurring canine spinal cord injury.
Canine intervertebral disk herniation (IVDH) is a common, naturally occurring form of spinal cord injury (SCI) that is increasingly being used in pre-clinical evaluation of therapies. Although IVDH bears critical similarities to human SCI with respect to lesion morphology, imaging features, and post-SCI treatment, limited data are available concerning secondary injury mechanisms. Here, we characterized cerebrospinal fluid (CSF) cytokines, and chemokines in dogs with acute, surgically treated, thoracolumbar IVDH (n=39) and healthy control dogs (n=21) to investigate early inflammatory events after SCI. A bioplex system was used to measure interleukin (IL)-2, -6, -7, -8, -10, -15, and -18, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), keratinocyte chemoattractant (KC)-like protein, IFN-γ-inducible protein-10, monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha. Cytokine and chemokine concentrations in the CSF of healthy and SCI dogs were compared and, in SCI dogs, were correlated to the duration of SCI, behavioral measures of injury severity at the time of sampling, and neurological outcome 42 days post-SCI as determined by a validated ordinal score. IL-8 concentration was significantly higher in SCI cases than healthy controls (p=0.0013) and was negatively correlated with the duration of SCI (p=0.042). CSF MCP-1 and KC-like protein were positively correlated with CSF microprotein concentration in dogs with SCI (p<0.0001 and p=0.004). CSF MCP-1 concentration was negatively associated with 42-day postinjury outcome (p<0.0001). Taken together, these data indicate that cytokines and chemokines present after SCI in humans and rodent models are associated with SCI pathogenesis in canine IVDH.
1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, Texas.
Amanda R
AR
Taylor
C Jane
CJ
Welsh
Colin
C
Young
Erich
E
Spoor
Sharon C
SC
Kerwin
John F
JF
Griffin
Gwendolyn J
GJ
Levine
Noah D
ND
Cohen
Jonathan M
JM
Levine
D000818:Animals; D016207:Cytokines / Q000134:cerebrospinal fluid / Q000276:immunology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000276:immunology*; D015601:Injury Severity Score; D007405:Intervertebral Disc Displacement / Q000134:cerebrospinal fluid*; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid / Q000276:immunology*; D013904:Thoracic Vertebrae / Q000473:pathology
D016207:Cytokines
inflammation; models of injury; neural injury