Nuclear factor I-A (Nfia) is central to the survival mechanism that preconditions brain cells to endure injury, according to Johns Hopkins scientists. Their study was conducted in mouse brain cells as well as whole animals. The finding appears in the June online edition of the Journal of Clinical Investigation.
In their experiments, the Johns Hopkins team exploited the fact that when mouse brain tissue is subjected to a stressful but nonlethal insult—the equivalent of stroke in a dish—a defense response occurs that protects cells challenged by a more severe insult. The researchers exposed the cells to short bursts of a toxic chemical and screened them for genes that turned on as a result of the insult. Nfia, a transcription factor, was part of the list of genes compiled.
Focusing on Nfia, the researchers increased its expression in the cells during exposure to the toxic chemical that induced preconditioning. Then they decreased Nfia expression, noting that cells deficient in Nfia didn't survive, but those with more of the Nfia protein fared much better.
In another series of experiments, this time using mice, the team injected a toxic chemical into the brains of a control group of normal mice and also into a group that had been genetically engineered to produce less than the normal amount of Nfia protein. The mutant mice lacking Nfia were much more susceptible to brain-cell death.