Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy

Abstract

BackgroundChronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs.Hypothesis/ObjectivesThat cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM‐affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)‐6 and monocyte chemoattractant protein‐1/chemokine ligand 2 (MCP‐1/CCL2).AnimalsClient‐owned GDs: 15 control, 15 CSM‐affected.MethodsProspective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti‐inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs.ResultsAffected GDs had significantly lower MCP‐1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85–161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68–260.11, P = .028). In affected GDs, MCP‐1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti‐inflammatory medications, disease duration, or disease severity. IL‐6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92–2.47, P < .001) in GDs with SC signal changes.Conclusions and Clinical ImportanceLower MCP‐1/CCL2 in CSM‐affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL‐6 in CSM‐affected GDs with SC signal changes suggests more severe inflammation in this group.

MicroRNA expression in the cerebrospinal fluid of dogs with and without cervical spondylomyelopathy

“…Cerebrospinal fluid samples were prospectively collected as part of a different study, and remaining CSF was banked for prospective evaluation of the miRNA expression profile of Great Danes. The study was conducted in accordance with the guidelines and with approval of the institution's Clinical Research Advisory Committee and the Institutional Animal Care and Use Committee.…”

“…The OA‐CSM affected dogs were identified and included in the study if they exhibited clinical signs and neurological examination findings consistent with a diagnosis of cervical myelopathy. All dogs included in the study underwent standardized gait grading, cerebellomedullary cistern CSF collection, and MRI of the cervical vertebral column. The OA‐CSM was confirmed on MRI by 2 investigators (P.M.V.…”

“…and D.V.). Spinal cord compression was graded as mild, moderate, or severe as previously described . The sites of spinal cord compression and the presence or absence of spinal cord signal changes were determined based on sagittal and transverse T2‐weighted images of all intervertebral disc spaces of the cervical vertebral column.…”

“…An aliquot of each CSF sample was evaluated by a board‐certified veterinary clinical pathologist to determine total nucleated cell count, red blood cell (RBC) count, protein concentration, and cytology findings. This technique was described previously as part of a different study . The remaining CSF aliquots were stored at −80°C for subsequent miRNA analysis.…”

“…A number of surgical and medical management techniques have been described for DA‐CSM, but surgical treatment has comparable long‐term survival to medical management and no important advances in treatment for dogs with OA‐CSM have been made in the last decade . Studies have investigated molecular factors thought to play a role in the pathogenesis of OA‐CSM in dogs, identifying dysregulation of inflammatory cytokines interleukin‐6, monocyte chemoattractant protein‐1, and chemokine ligand 2 and alterations in vitamin‐D binding protein, angiotensinogen, and complement C3 proteins . A better understanding of the pathophysiology and mechanisms underlying OA‐CSM will be critical to identify potential targets for treatment and develop biomarkers to monitor response to treatment and to identify treatment responders.…”