Cerebrospinal Fluid Inflammatory Cytokines and Chemokines in Naturally Occurring Canine Spinal Cord Injury

Abstract

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-c), keratinocyte chemoattractant (KC)-like protein, IFN-c-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.

Posttraumatic Inflammation as a Key to Neuroregeneration after Traumatic Spinal Cord Injury

“…Apart from these studies, Kwon et al [ 5 ] indicated a positive correlation between IL-6 and IL-8 CSF levels and the severity of neurological impairment. These results were affirmed in further animal studies [ 10 , 21 ]. Unfortunately, they did not have a follow-up and, therefore, could not study the regenerative aspect of different factors.…”

Factors associated with recovery from paraplegia in dogs with loss of pain perception in the pelvic limbs following intervertebral disk herniation

“…[20][21][22] However, neither of those methods alone provides prognostic accuracy superior to that of testing for deep pain perception. Measurement of various biomarker concentrations in serum or CSF [23][24][25][26] holds considerable promise for future prognostication but is insufficiently sensitive and specific at present.…”

Time course and prognostic value of serum GFAP, pNFH, and S100β concentrations in dogs with complete spinal cord injury because of intervertebral disc extrusion

“…By contrast, dogs with complete injuries (paraplegic with no pain sensation in either hind limb or tail) have a 50%‐60% chance of recovery that cannot be reliably predicted from the neurological examination . Many groups have evaluated different prognostic biomarkers in this group of dogs including quantification of magnetic resonance imaging (MRI) findings, and measurement of inflammatory mediators and neural proteins found in cerebrospinal fluid (CSF) . Although useful, these approaches involve considerable cost (MRI) and are clinically invasive (CSF sampling).…”