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.

Utility of C‐reactive protein and serum amyloid A in the diagnosis of equine protozoal myeloencephalitis

“…An increase in CRP concentration in CSF is thought to largely result from blood‐brain barrier damage (ex. subarachnoid hemorrhage6 or vasculitis due to sepsis17); intrathecal production of CRP18 and disruption of glymphatic circulation may also contribute to a lesser extent 19. Even when the blood–brain barrier is intact CRP level in the CSF is directly related to serum CRP because this protein flows from blood into the cerebrospinal space,20 but determination of a CRP index along with IgG index has been proposed in cases of canine Steroid Responsive Meningitis‐Arteritis (SRMA)6 and may also be helpful in cases of blood–brain barrier disruption in equine neurological disease.…”

Acute phase proteins in serum and cerebrospinal fluid in healthy cattle: possible use for assessment of neurological diseases

“…In dogs, an increase of Hp in the CFS was demonstrated in animals with naturally occurring intervertebral disc herniation (IVDH) compared to healthy dogs (Anderson et al 2015). In the same study, dogs with severe spinal cord injury showed significantly higher concentration of Hp in the CSF than animals with slight to moderate injuries.…”

“…A positive correlation was observed between the ceruloplasmin concentration in the CSF and the severity of spinal cord injuries in dogs with IVDH (Anderson et al 2015). Ceruloplasmin was also correlated with the concentration of total proteins in the CSF, signaling rupture of the brain-blood barrier.…”

“…However, no correlation was found between the Hp concentration in the CSF and the motor, posture or sensory results. Hp was considered the most important APP of the CSF after injury associated with IVDH in the dogs studied (Anderson et al 2015). In humans, the concentration of Hp in the CSF was also found to be significantly higher after traumatic brain injury.…”

“…Another study concluded that CSF APPs estimation is a useful marker to differentiate pyogenic from non-pyogenic meningitis, but it cannot differentiate between tuberculosis and fungal or viral meningitis (Anil Kumar et al 2010). In turn, it has been demonstrated that the level of APPs is significantly greater in the CSF of dogs with acute spinal cord injury compared with healthy control dogs (Anderson et al 2015). CSF APPs levels were positively associated with the severity of spinal cord damage and can serve as a prognostic indicator in dogs with intervertebral disc herniation (Roerig et al 2013).…”