Abbracchio's work combines two emerging trends--a biochemical focus on a cellular gate known as a GPCR (for G-protein-coupled receptor) and a neuroscientific focus on glial cells. GPCRs were shown in the 1990s to play key roles in admitting signals through cell walls of all sorts, thus controlling cellular behavior. Hundreds of types of GPCRs serve as gatekeepers around the body. Scientists figured that if they could find the keys that open crucial cellular gates, they might alter cell behaviors that do damage in disease or injury.
This was precisely Abbracchio's approach. She knew that ATP, a major chemical transmitter, was released in great quantities after a stroke, and that glial cells called astrocytes and microglia responded by swarming the injury site to clean up. Glial cells, of which there are several types, outnumber neurons nine to one; research in the labs of Abbracchio, Fields and many others are proving them to be crucial to many brain functions. Unfortunately, the glia swarming a stroke site don't just clean up; they also kill other glial cells as well as neurons, inflicting most of the stroke's actual damage.
Abbracchio found one particular GPCR--GPR17, which responded to ATP--that was widespread, and amassed in numbers after stroke damage. She also found that GPR17 was sensitive to cysteinuyl-leukotrienes, fatty, hormonelike molecules known to be active in causing inflammation. This dual responsiveness at GPR17 was itself news, as researchers had previously thought that each GPRC opened to only one key. That insight could pay other dividends later. In the meantime, the bigger news is that when Abbracchio developed ways to block both the action and post-stroke spread of GPR17 in rats in which she induced strokes (by tying off the middle carotid artery), she found that doing so even as late as an hour after the stroke almost completely eliminated the damage.
Abbracchio is now working to try see if the technique might transfer to human stroke victims--keeping in mind the usual caveats about concluding too much from animal studies. "There's a lot we still don't know," she remarks. "We don't know what these receptors do on normal days, for instance. But it's clear they play a big role in stroke damage. The ability to control this in rats is clearly encouraging."