Researchers from North Carolina State University have found that blood serum concentrations of both neuroproteins and neurosteroids are associated with neonatal maladjustment syndrome (NMS) in newborn foals. The work could lead to better diagnostic tools and potential therapies.
“Neonatal maladjustment syndrome is a very complex disease in neonatal foals,” says Katarzyna Dembek, associate professor of clinical sciences at NC State and corresponding author of the research. “Foals with NMS usually develop neurological signs at birth or within the first 24-48 hours after birth. When you rule out brain damage from foaling, many of those foals with NMS can recover. But the mechanism behind the disease is not completely understood.”
While clinical signs of NMS are variable, the most common one is lack of a normal nursing reflex. On the more severe side, foals can develop seizures and become comatose. Treatment consists primarily of using a feeding tube or teaching the foal to drink from a bucket until they can be weaned, as well as providing supportive care for more severe cases.
Dembek’s team were specifically interested in three neuroproteins, two of which are produced by astrocytes, or brain cells that support the nervous system. These neuroproteins, brain-derived neurotrophic factor (BDNF), glial-fibrillary-acidic protein (GFAP), and astrocytic protein S100B, are used for diagnosis of several different neurological diseases such as Parkinson’s disease or neonatal encephalopathy in people but haven’t been studied in foals with neurological symptoms.
The team took blood serum and plasma measurements from 14 healthy and 58 hospitalized foals. Of the hospitalized foals, 19 were NMS foals, while the others presented with different diseases, such as sepsis or diarrhea. Blood serum was measured at admission, and again at days one and two of hospitalization.
In addition to the neuroproteins, the team measured the levels of three pregnanes, or neurosteroids that are produced in the brain and can affect neuronal function. These neurosteroids are metabolites of progesterone, a pregnancy hormone, and have been detected at high levels in the brains of both normal foals and foals with NMS.
“The difference is, while normal healthy foals have high concentrations of those progesterone-derived steroids, the levels decrease very quickly,” Dembek says. “Within 24-48 hours, they’re unmeasurable. However, foals with neurological signs retain that high concentration for days. We measured the pregnane levels in addition to the proteins to confirm NMS in the foals.”
They saw that the pregnane levels remained high in NMS foals compared to both healthy and sick foals. For the neuroproteins, they saw that BDNF concentration decreased over the first day of hospitalization in NMS foals, S100B was higher in septic foals with NMS compared to septic foals without NMS, and GFAP concentration was lower in NMS and sick foals compared to healthy foals.
“I think that the main finding here is that pregnanes and these neuroproteins – particularly BDNF and S100B – could serve as biomarkers of not only NMS, but prematurity and sepsis as well,” Dembek says. “Further research is necessary to establish practical applications for S100B and BDNF in clinical settings and to fully understand the dynamics of these biomarkers.”
The work appears in the Journal of Veterinary Internal Medicine and was supported by the Morris Animal Foundation. Javier Perez, former resident at NC State who is currently at Veterinary Associates Equine, New Zealand, is the first author. Other contributors include Kinnidy Coley, Adoption Center, ASPCA, New York; David Wong of Iowa State University; Nimet Browne of the Hagyard Equine Medical Institute; and Myriah Albrecht of Hagyard Equine Medical Institute.
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