Protecting newborns from brain damage

Snyder, a neonatologist and pediatric neurologist, has long envisioned using human neural stem cells to protect newborns with acute perinatal HII from brain damage. He and his colleagues made the discovery that MRI could be used as an objective, quantifiable, readily available basis for inclusion and exclusion criteria for this treatment while engaged in preclinical studies required prior to starting human clinical trials for babies with HII. This birth injury affects two to four newborns out of every 1,000 babies born in the U.S. and is attributable to a number of complications, including umbilical cord compression, disrupted maternal blood pressure and maternal infection.


“My hope is that human neural stem cells can help rescue enough injured and vulnerable—though not dead—neural cells,” explains Snyder. “This could help prevent the most severely affected infants from developing cerebral palsy, epilepsy, intellectual disability or other neurological disorders that often arise after HII if left untreated.”

In the study, the scientists used MRI to measure two areas surrounding the regions of HII brain injury in rats: the penumbra, a region that consists of mildly injured, “stunned” neurons; and the core, an area that consists of dead neurons. They found that rats with a larger penumbra and smaller core that received human neural stem cells had better neurological outcomes—including improved memory—demonstrated by the ability to swim to a hidden platform (Morris Water Maze test), and a greater willingness to venture into a brightly lit area (open field test).

In these rats, the penumbra—to which the neural stem cells homed avidly—became normal tissue (based on MRI and histological standards), while the core remained unimproved and attracted few cells. Penumbra that did not receive cells became part of the core, populated by dead neurons—indicating the benefit of the stem cell treatment.

“This approach to brain lesion classification is a powerful patient stratification tool that allows us to identify newborns who may benefit from this stem cell therapy—and protect others from undergoing unnecessary treatment,” says Snyder. “Based on our findings, only newborns with a large penumbral volume in relation to core volume should receive a transplant of human neural stem cells. Equally important, newborns so severely injured that only a core is present, or babies with such a mild case of HII that not even a penumbra is present, should not receive human neural stem cells, as the treatment is unlikely to be impactful.”

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