title: Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury.
abstract: Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target.
authors.affiliation: 1 Department of Small Animal Clinical Sciences, Texas A&M University , College Station, Texas.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Anderson
authors.affiliation: 2 Department of Veterinary Integrative Biosciences, Texas A&M University , College Station, Texas.
authors.forename: C Jane
authors.initials: CJ
authors.lastname: Welsh
authors.affiliation: 2 Department of Veterinary Integrative Biosciences, Texas A&M University , College Station, Texas.
authors.forename: Colin
authors.initials: C
authors.lastname: Young
authors.affiliation: 4 Department of Veterinary Pathobiology, Texas A&M University , College Station, Texas.
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: Levine
authors.affiliation: 1 Department of Small Animal Clinical Sciences, Texas A&M University , College Station, Texas.
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Kerwin
authors.affiliation: 1 Department of Small Animal Clinical Sciences, Texas A&M University , College Station, Texas.
authors.forename: C Elizabeth
authors.initials: CE
authors.lastname: Boudreau
authors.affiliation: 2 Department of Veterinary Integrative Biosciences, Texas A&M University , College Station, Texas.
authors.forename: Ismael
authors.initials: I
authors.lastname: Reyes
authors.affiliation: 2 Department of Veterinary Integrative Biosciences, Texas A&M University , College Station, Texas.
authors.forename: Armando
authors.initials: A
authors.lastname: Mondragon
authors.affiliation: 3 Department of Large Animal Clinical Sciences, Texas A&M University , College Station, Texas.
authors.forename: John F
authors.initials: JF
authors.lastname: Griffin
authors.affiliation: 3 Department of Large Animal Clinical Sciences, Texas A&M University , College Station, Texas.
authors.forename: Noah D
authors.initials: ND
authors.lastname: Cohen
authors.affiliation: 1 Department of Small Animal Clinical Sciences, Texas A&M University , College Station, Texas.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Levine
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002097:C-Reactive Protein / Q000134:cerebrospinal fluid*; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000134:cerebrospinal fluid*; D004285:Dogs; D006242:Haptoglobins / Q000134:cerebrospinal fluid*; D007405:Intervertebral Disc Displacement / Q000134:cerebrospinal fluid*; D009961:Orosomucoid / Q000134:cerebrospinal fluid*; D000685:Serum Amyloid A Protein / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D006242:Haptoglobins; D009961:Orosomucoid; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein
keywords: biomarkers; canine; neurotrauma; secondary injury