Measurement of 8-hydroxy-2'-deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia.
Authors: Palmisano Megan, Kulp Jeaneen, Bender Susan, Stefanovski Darko, Robinson Mary, Johnson Amy
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary: Oxidative Stress Markers in Equine Neuroaxonal Degeneration Researchers investigated whether 8-hydroxy-2'-deoxyguanosine (8-OHdG), a well-established marker of oxidative DNA damage in human neurodegeneration, could differentiate horses with neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) from those with other neurological conditions or normal controls. Using biobanked serum and cerebrospinal fluid samples collected over a 12-year period from 50 postmortem-confirmed cases (20 NAD/DM, 10 cervical vertebral stenotic myelopathy, 10 equine protozoal myeloencephalitis, and 10 controls), they measured 8-OHdG concentrations via highly sensitive ELISA and compared values between diagnostic groups. Contrary to expectations, CSF and serum 8-OHdG levels showed no statistically significant differences between NAD/DM horses and other groups—NAD/DM horses had a median CSF concentration of 169.9 pg/mL versus 157.1 pg/mL (CVSM), 131.4 pg/mL (EPM), and 149.8 pg/mL (controls)—and Poisson regression analysis controlling for confounding variables confirmed no meaningful diagnostic associations. These findings suggest that oxidative stress may not be the dominant pathophysiological mechanism at the point of clinical diagnosis, or alternatively, that 8-OHdG is insufficiently sensitive as an antemortem biomarker in equine neurological disease; clinicians should therefore not rely on this marker for diagnostic differentiation of NAD/DM
Read the full abstract on PubMed
Practical Takeaways
- •8-OHdG measurement in serum or CSF cannot be used as a diagnostic tool to antemortem diagnose NAD/DM in clinical practice
- •Clinicians should not rely on oxidative stress biomarkers to differentiate NAD/DM from other causes of proprioceptive ataxia such as CVSM or EPM
- •Additional diagnostic methods beyond oxidative stress markers will be needed to improve antemortem diagnosis of this degenerative neurologic condition in horses
Key Findings
- •8-OHdG concentrations in CSF and serum did not significantly differ between NAD/DM horses (CSF median 169.9 pg/mL, serum 130 pg/mL) and other neurologic disease groups or controls
- •Poisson regression analysis showed no significant differences in 8-OHdG levels once confounding variables were considered
- •8-OHdG failed to serve as a biomarker for antemortem diagnosis of NAD/DM in this cohort
- •Study concludes horses with NAD/DM do not have ongoing oxidative stress detectable via 8-OHdG at the time of diagnosis