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. 2016 Jun 10;17(1):31.
doi: 10.1186/s12868-016-0269-4.

Arachidonic acid pathway alterations in cerebrospinal fluid of dogs with naturally occurring spinal cord injury

Rae L Russell  1   2 , Jonathan M Levine  1 , Nick D Jeffery  3 , Colin Young  2 , Armando Mondragon  2 , Bryan Lee  2 , C Elizabeth Boudreau  1 , C Jane Welsh  2 , Gwendolyn J Levine  4
Affiliations

Arachidonic acid pathway alterations in cerebrospinal fluid of dogs with naturally occurring spinal cord injury

Rae L Russell et al. BMC Neurosci. .

Abstract

Background: Canine intervertebral disc πherniation causes a naturally-occurring spinal cord injury (SCI) that bears critical similarities to human SCI with respect to both injury pathomechanisms and treatment. As such, it has tremendous potential to enhance our understanding of injury biology and the preclinical evaluation of novel therapies. Currently, there is limited understanding of the role of arachidonic acid metabolites in canine SCI.

Results: The CSF concentrations of PLA2 and PGE2 were higher in SCI dogs compared to control dogs (p = 0.0370 and 0.0273, respectively), but CSF LCT4 concentration in SCI dogs was significantly lower than that in control dogs (p < 0.0001). Prostaglandin E2 concentration in the CSF was significantly and positively associated with increased severity of SCI at the time of sampling (p = 0.041) and recovery 42 days post-injury (p = 0.006), as measured by ordinal behavioral scores.

Conclusion: Arachidonic acid metabolism is altered in dogs with SCI, and these data suggest that these AA metabolites reflect injury severity and recovery, paralleling data from other model systems.

Keywords: Canine; Neurotrauma; Phospholipase A2; Prostaglandin E2.

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Figures

Fig. 1
Fig. 1
Scatter plots and line and whisker plots summarizing concentrations of AA metabolites in CSF of 44 dogs with SCI and 21 control dogs. There was a significantly higher CSF PLA2 concentration in dogs with SCI compared to control dogs (asterisks, p = 0.0370) (a). The concentration of LCT4 in the CSF of SCI dogs was significantly lower than that in control dogs (asterisks, p < 0.0001) (b). The concentration of PGE2 in the CSF of SCI dogs was significantly higher (c, asterisks, p = 0.0273) compared to that in control dogs (<31 pg/mL, dotted line)
Fig. 2
Fig. 2
Linear regressions amongst CSF AA pathway metabolite concentrations and total nucleated cell counts (TNCC, cells/µL), CSF total protein (mg/dL), and CSF red blood cell count (cells/µL) in 44 SCI dogs. PLA2 concentration was negatively associated with TNCC in dogs with SCI (r2 = 0.178, slope = −0.400; p = 0.004) (a). CSF PGE2 concentration correlated positively with CSF total protein concentration (b, r2 = 0.422, slope = 3.75; p < 0.0001), and CSF RBC (c, R2 = 0.451, slope = 0.370; p < 0.0001)
Fig. 3
Fig. 3
Linear regressions of CSF AA pathway metabolites and modified Frankel scores (MFS) at day of hospital admission (day 0). PLA2 and LTC4 were not significantly correlated to MFS at day 0 (r2 = 0.0004, slope = −0.221; p = 0.894, and r2 = 0.012, slope = 0.–2.23; p = 0.4756, respectively) (a, b). PGE2 was higher in SCI dogs with lower MFS at day 0 (r2 = 0.137, slope = − 23.9; p = 0.013) (c)
Fig. 4
Fig. 4
Linear regressions of AA pathway metabolites and Texas Spinal Cord Injury Scores (TSCIS) at day 42 post-injury. PLA2 and LTC4 were not significantly correlated to TSCIS at day 42 (r2 = 0.00003, slope = −0.021; p = 0.970, and r2 = 0.030, slope = 0.–1.166; p = 0.262, respectively) (a, b). PGE2 was significantly correlated to lower TSCIS at day 42 in dogs with SCI (r2 = 0.199, slope = −9.62; p = 0.002) (c)
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