November/December 1998 THIS MONTH'S ISSUE: Social Sciences Ecology Wildlife Biology Bioethics Neuroscience INDEX |
Frontiers in
Neuroscience The brain may be a marvel of creation, but its awesome complexity and sophisticated functioning have been bought, in evolutionary terms, by a greatly diminished capacity for regeneration and repair. Once damaged by injury or disease, neurons in the central nervous system (CNS) — the brain and spinal cord — have difficulty knitting themselves together to re-establish normal working connections. Yet when placed in the peripheral nervous system, these cells are able to grow for long distances. “The capacity for regeneration is there, but something is preventing it, at least in higher vertebrates,” neuroscientist Diana Lurie says. According to Lurie, an assistant professor of neuropharmacology in the Department of Pharmaceutical Sciences at UM, that something has to do with the chemical environment surrounding the severed neurons, not the physical barrier presented by the lesion itself. Cell signals Using rat and chick brains as models, she focuses her work on glial cells, of which there are many kinds. Glial cells surround neurons, providing nourishment, removing toxins and regulating cell communication. Following injury, glial cells called astrocytes start to divide, and this increase is part of what forms a scar. But not all astrocytes divide, Lurie says, or else the scar would become huge and tumor-like. She has discovered that the enzyme known as SHP-1, present in many body tissues, appears at greatly elevated levels in some CNS astrocytes after injury. She further observed that astrocytes containing SHP-1 do not seem to divide. “The hypothesis is that SHP-1, which we know plays a basic role in switching cell functions on and off, may be keeping the scar from growing out of control,” Lurie says. The question now is whether cells with SHP-1 release other chemicals that help or hinder regeneration. Researchers know that astrocytes produce chemical compounds that both promote and inhibit regeneration, but do not know which cells produce which compound. Identifying astrocytes that produce SHP-1 may advance that research. In the past, she says, a scientist might injure a rat spinal cord, for example, and then “throw in all kinds of different substances to see if they would help regeneration.” Nothing much really worked, so researchers decided it was time to step back and look at the basic mechanisms of what happens after injury and use that information to design a therapy. To this end, Lurie has been wondering whether the SHP-1 enzyme would have the same dampening effect on tumors as it does on scar formation. A newly formed partnership between UM and St. Patrick Hospital in Missoula is offering her a chance to find out. Diagnostic potential Glial cell tumors are one of the most common forms of brain cancer, Lurie says. They are challenging to treat because very few prognostic markers exist to tell doctors whether a particular tumor will be aggressive or slow-growing or whether it will respond to radiation or chemotherapy. Lurie screens samples of malignant tumors taken from patients at St. Patrick Hospital for the presence of the SHP-1 enzyme and correlates its level with how well the patient fared. In this way, the enzyme might be used to predict how a glial tumor will grow and respond to therapy. In almost all samples screened so far, Lurie has found a lot of the SHP-1 enzyme. One sample contained very little enzyme and turned out to be from a patient with a very slow-growing tumor. Lurie hypothesizes that cells in slow-growing tumors are dividing less and therefore need less of the chemicals that control growth and hence less of SHP-1. The results to date, based on such a small sample, are not data, Lurie says; “they’re a miracle.” Nevertheless, they are suggestive. Her ultimate hope, if such correlations continue, is that screening tumors for SHP-1 will become routine and the results used to help identify the best treatment. “The goal of any biomedical research is to develop a therapy,” Lurie says. “For me that therapy would be to improve or even get significant functional central nervous system recovery after injury.” |
