Understanding causes of neurological abnormalities in premature birth
In the February issue of the American Journal of Pathology, new research from the University of Chicago shows motor abnormalities frequently associated with low birth weight babies could originate due to peripheral nerve defects.
"There has been a lot of focus on the central nervous system and we know that these infants do not myelinate the brain well, meaning they don't produce the multi-layer membrane that surrounds nerve cells as robustly as normal birth weight babies," explained study author Brian Popko, PhD, Jack Miller Professor of Neurological Disorders in the Department of Neurology and Director of the University of Chicago Center for Peripheral Neuropathy.
The study suggests that preterm infants may experience delayed development and myelination of the peripheral nervous system that could contribute to motor and neurological deficits experienced in adulthood, according to the lead author Ben Clayton, PhD, a former graduate student in Popko's lab.
"It is well known that hypoxia (low oxygen) experienced by preterm infants can disrupt or lead to delayed myelination of the central nervous system. This led me to wonder whether hypoxia could have a similar effect on the peripheral nervous system," said Clayton.
Hypoxia is associated with premature and low birth weight babies, weighing in the range of 2.2 to 3.3 pounds.
"It is thought the reason that there are these abnormalities within the central nervous system is secondary to the fact that they are not as well oxygenated as a normal birth weight baby because their lungs have not developed to the extent that normal birth weight babies do," said Popko.
Due to advances in medicine and treatment many of these infants now survive, but with new complications stemming from developmental abnormalities. Researchers are now trying to understand the link between hypoxia, myelination, and the observed nervous system defects.
According to Popko, the amount of myelin an organism has at birth reflects on what it can do.
"Horses are well myelinated at birth and are basically born ready to run, humans are born with some amount of myelin, and mice are born without any myelin," said Popko. "So, in a sense, mice are born prematurely relative to humans and that's why mice are a good model of premature birth."
The myelin sheath helps promote rapid nerve conduction. When it is thinner the nerve conduction is diminished, causing neurological abnormalities.
Popko and Clayton found that the peripheral nerves do not myelinate well when newborn mice are exposed to hypoxic conditions. This myelination defect persists into adulthood and is correlated with nerve abnormalities, similar to what happens in the central nervous system.
"Our peripheral nerves are there to control our muscles and the mice also show diminished strength that correlates with the nerve abnormalities," said Popko.
According to Clayton, it would be of interest to determine if their findings in mice are similar to what happens with the peripheral nerves of human premature infants.
"This study suggests that the motor abnormalities that low birth weight babies develop could originate due to peripheral nerve defects as well as central nervous system defects," said Popko. "We need to take this into consideration when we are thinking about therapeutic approaches."
This study was funded by the National Institutes of Health. Additional authors include Aaron Huang, Danuta Dukala, and Betty Soliven from the University of Chicago.