A close look at white matter
"Use your grey matter!" Although it's not an expression that we hear a lot any more, it points to the kind of snobbery around the two types of brain tissue: grey matter and white matter. Grey matter, where the cell bodies of the neurons are located, has long been considered the "important" part of the brain where all the interesting stuff occurs. The white matter, which is made up of the axons (long filaments that extend from the neuron cell bodies), was considered less critical to brain function.
Not true, says Dr. Peter Stys, a brain researcher and stroke neurologist at the University of Calgary. "The white matter has all the connections. If there was no white matter, our brains would be working computers that couldn't talk to the outside world." Dr. Stys says the lack of knowledge about white matter may be one of the reasons many stroke treatments developed in the lab have had disappointing results in the clinic. "Most treatments are directed at the grey matter neurons without consideration for the connections in the white matter. If these tissues respond differently to stroke, then a drug targeted only at grey matter will not work."
For the past 20 years, Dr. Stys has dedicated his research to finding out how white matter functions. His approach is to identify the molecules, channels, and proteins that function abnormally in diseases like multiple sclerosis, spinal cord injury, and stroke. Advanced laser scanning imaging techniques are used to see individual cells and components of nerve fibres in slices of brain tissue from rats and mice.
His team has made significant inroads. In 1992, Dr. Stys proposed a three-step series of molecular mechanisms, which is called a cascade reaction because the series continues to the end once the initial step occurs, that result in injury to axons. Since then, he has added about 25 more steps in the series. Interestingly, although spinal cord injury, stroke, and multiple sclerosis are very different from the perspective of the patient, there is a tremendous degree of overlap in the cascades that damage white matter. What this might mean is that a drug treatment developed for protecting white matter in one type of disorder may well work for the others as well. Recent experiments in Dr. Stys's lab indicate that this may be so.
"Mother Nature has given us a very complex problem in white matter damage," he says. "If we want to solve it, we're going to have to work through this complexity, whether we like it or not. The key thing is that there are bottlenecks, where cascades cross over at certain steps. If we have a logical map that is true to reality, we can distil all the steps into one, two, or three critical ones and go after them with drugs."