Matrix metalloproteinase-9 activity in the cerebrospinal fluid and serum of dogs with acute spinal cord trauma from intervertebral disk disease

Levine, Jonathan M.; Ruaux, Craig G.; Bergman, Robert L.; Coates, Joan R.; Steiner, Jörg M.; Williams, David A.

doi:10.2460/ajvr.67.2.283

Cited by 68 publications

(69 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both the MFS 23 and CSF MBP concentration 13 have been previously associated with functional recovery in dogs with thoracolumbar IVDH and were shown via the logistic regression analysis to be independently related to outcome within the dogs in the present study; details of the findings regarding MBP concentration have been communicated in another report 13 about the same group of dogs. The collective impact of CSF CK activity, CSF MBP concentration, and MFS depends on case characteristics.…”

Section: Discussionmentioning

confidence: 49%

“…Neurologic dysfunction was classified according to the MFS as follows: paraspinal hyperesthesia only (grade 5), ambulatory paraparesis and ataxia (grade 4), nonambulatory paraparesis (grade 3), paraplegia with intact nociception (grade 2), paraplegia with no superficial nociception (grade 1), and paraplegia with no deep nociception (grade 0). 22,23 After premedication of each affected dog, anesthesia was induced via IV administration of propofol a and anesthesia was maintained by use of inhalation anesthetic agents (sevoflurane b or isoflurane c ) for diagnostic imaging and collection of a CSF sample from the cerebromedullary cistern. Advanced imaging comprised myelography, computed tomography, or MR imaging; the type of imaging performed depended on access to equipment and clinician preference.…”

Section: Dogs With Acute Thoracolumbar Ivdh-betweenmentioning

confidence: 99%

See 1 more Smart Citation

Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation

Witsberger¹,

Levine²,

Fosgate³

et al. 2012

javma

Self Cite

View full text Add to dashboard Cite

Objective—To examine associations between CSF biomarkers, initial neurologic dysfunction, and long-term ambulatory outcome in dogs with acute intervertebral disk herniation (IVDH). Design—Prospective clinical study. Animals—54 dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. Procedures—For each dog, variables, including CSF myelin basic protein (MBP), lactate, calcium, glucose, and total protein concentrations; nucleated cell count; and creatine kinase (CK) and aspartate aminotransferase activities, were measured. For dogs with thoracolumbar IVDH, initial neurologic function was characterized by use of a modified Frankel score (MFS; determined on a scale of 0 to 5, where 0 represented paraplegia with no deep nociception and 5 represented paraspinal hyperesthesia only). Long-term follow-up was assessed. Results—Among dogs with thoracolumbar IVDH, those with CSF CK activity ≤ 38 U/L had a 35-fold increase in the odds of long-term ambulation, compared with the odds in dogs with CSF CK activity > 38 U/L, adjusting for neurologic functioning at the evaluation. The CSF lactate, calcium, and glucose concentrations and aspartate aminotransferase activity were not predictive of long-term ambulatory outcome. Data analysis revealed that long-term functional recovery was > 98% for affected dogs, regardless of their initial MFS, when CSF CK activity was ≤ 38 U/L and MBP concentration was ≤ 3 ng/mL. Conclusions and Clinical Relevance—In dogs with acute thoracolumbar IVDH, CSF CK activity and MBP concentration appeared to be prognostic indicators and, along with initial MFS, can be used to predict long-term ambulatory outcome.

show abstract

Section: Discussionmentioning

confidence: 49%

Section: Dogs With Acute Thoracolumbar Ivdh-betweenmentioning

confidence: 99%

Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation

Witsberger¹,

Levine²,

Fosgate³

et al. 2012

javma

Self Cite

View full text Add to dashboard Cite

show abstract

“…Reported cerebrospinal fluid biomarkers include aspartate aminotransferase, calcium, glucose, nucleated cell count, protein, creatine kinase, lactate, myelin basic protein, matrix metalloproteinase 9, and tau protein. 139,[142][143][144][145][146][147][148][149] Witsberger and colleagues 139 published a screening method for clinical cases of acute SCI. In this study, combined elevation of myelin basic protein and creatine kinase in dogs with no detectable pain sensation following IVDH led to the probability of a successful outcome of 10%.…”

Section: Biomarkersmentioning

confidence: 99%

Acute Spinal Cord Injury

Granger

Carwardine

2014

Veterinary Clinics of North America: Small Animal Practice

View full text Add to dashboard Cite

“…7 A small group of studies has demonstrated that inflammatory mechanisms may play a critical role in canine IVDH-associated SCI. [8][9][10][11] In particular, in acute canine SCI, resident microglial activation is prominent as is upregulation of matrix metalloproteinase 9, release of myelin basic protein, and overproduction of interleukin (IL)-6 and IL-8 messenger RNA (mRNA). [9][10][11][12] In order to further develop this model system, a broader understanding of inflammatory mechanisms after SCI is needed, particularly if pathways are to be targeted in preclinical trials.…”

Section: Introductionmentioning

confidence: 99%

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

Taylor

Welsh²,

Young³

et al. 2014

Journal of Neurotrauma

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Matrix metalloproteinase-9 activity in the cerebrospinal fluid and serum of dogs with acute spinal cord trauma from intervertebral disk disease

Abstract: Data were consistent with results of experimental rodent spinal cord injury studies that indicate that MMP-9 is expressed early during secondary injury.

Cited by 68 publications

References 24 publications

Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation

Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation

Acute Spinal Cord Injury

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

Contact Info

Product

Resources

About