MUSC Researchers Take Aim at Strokes in Low Birthweight Infants

Researchers at the Medical University of South Carolina are using mice models to design better treatments for babies born with low birthweight who suffer a germinal matrix hemorrhage (GMH).

Thousands of children are born with very low birthweight in the US every year, and many are at high risk of suffering a brain hemorrhage, called a germinal matrix hemorrhage (GMH), shortly after birth, causing severe long-term health effects or death.

Researchers at the Medical University of South Carolina (MUSC) are turning to mice to develop new strategies for diagnosing and treating the condition, an effort that could greatly improve the birth rate and reduce the number of birth defects.

“We were just having to wait for bad things to happen,” Ramin Eskandari, MD, a pediatric neurosurgeon at MUSC Children’s Health, said in a recent press release. “And then we had to react to them. We have no treatment for the actual hemorrhage or for preventing the stroke or hydrocephalus that comes after.”

Eskandari said he came upon research by Stephen Tomlinson, PhD, vice chair of the Department of Microbiology and Immunology at MUSC, who was focusing on a part of the immune system called the complement system. Thinking that work could have applications for infants, the two collaborated with Mohammed Alshareef, MD, a senior neurosurgery resident at MUSC, to create a mouse model to stand in for premature infants with very low birthweight.

In a study recently published in the International Journal of Molecular Sciences, the team found that they could inhibit the complement system in the brain immediately after a hemorrhage, reducing and possibly even preventing temporary and permanent damage that accompany these types of strokes. By using a complement inhibitor called CR2Cry, they found improve not only survival but weight gain, reduce brain injury and incidents of hydrocephalus, an improve motor and cognitive performance in adolescence.

The new treatment could have a profound effect on the survival rate and long-term health for babies born with very low birthweight, who made up about 1% of infants born in the US in 2020, or roughly 48,500 births. And those numbers are rising as healthcare providers use new technology and treatments to treat newborns.

“We’re seeing younger and younger babies viable,” Eskandari said in the press release. “I remember when a 23-week-old baby wasn’t viable, and even in the last eight years since my residency, we’re now seeing babies at 20 weeks not only be viable but live full lives and attend school.” 

The process that Eskandari and his colleagues developed is unique in the more than 100 clinical trials currently running, because it targets a specific part of the brain. But focusing on the point where the pathology begins, they can avoid affecting the complement system for the entire body, thus reducing the chance of infection and other immune disorders.

Eskandari and his colleagues say their research will not only help infants born with brain hemorrhages, but those dealing with other types of brain injury as well.

“These babies are a really good overall model of how all brain injury could potentially be helped,” he said, adding that he hopes to launch a clinical trial soon at MUSC. “Having a hemorrhage that leads to stroke and hydrocephalus checks a lot of boxes that we see in many patients.”