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Many questions remain. “We still don’t know enough about this particular drug’s toxicity—especially in young children,” Rowitch says. “And, I think it would be simplistic to think this pathway is the only thing going on in the inhibition of myelin repair.” Still, he says, the results suggest it might be possible to speed mending of tattered myelin with a drug soon after injury, before the underlying axon is permanently harmed.
Where and When Development Occurs
“Every baby’s brain contains a variety of immature precursor cells that could, in theory, be enlisted to help mend injuries,” says Rowitch. But first scientists need to know more about how and what these cells do. To that end, he has been collaborating with UCSF neural stem cell biologist Arturo Alvarez-Buylla and neurosurgeon and postdoctoral fellow Nader Sanai, now at Barrow Neurological Institute in Phoenix, to map the trajectory of human stem cell activity emanating from a rich pocket of neurogenesis in the brain known as the subventricular zone (SVZ).
The SVZ has been well characterized in mice, in nonhuman primates, and, to a lesser extent, in human fetuses and older adults. But no one knew if or how activity in that region changed over the course of brain development in newborns and young children.
Now, by carefully comparing the cellular architecture of brain tissue from 54 infants, young children, and teens, Rowitch, Sanai, and Alvarez-Buylla have begun filling that information gap—and turning up surprises. For one thing, at least some of the stem cells arising from the SVZ travel to a different region in the human brain than in the mouse brain.
“In humans we’re seeing streams of cells from the SVZ moving not just into the olfactory bulb but also toward the frontal cortex,” says Sanai, who was an HHMI fellow during his medical school training at UCSF. “That newly discovered pathway raises questions about the mechanics of how the brain developed and evolved.”
Another dramatic twist: after a period of robust neurogenesis in the first year of life, the human SVZ apparently slows down, sharply tapering production of brain cells by the time a child is 18 months old, and then slowing to almost zero by age two. The finding should help settle conflicting earlier reports, say Sanai and Rowitch, that suggested the SVZ might churn out new cells well into adulthood. The results were reported October 20, 2011, in Nature.
The first year of life is a window of particular vulnerability and opportunity for the brain, says Rowitch. It’s a period of tremendous growth, organization, and flexibility, as fresh neural connections are created, broken, and remade. A better understanding of how things can go wrong in that critical period, he says, could ultimately improve the chances that things will go right.