Research

The lab's major research interest is neonatal brain injury, in particular the ischemic injury that underlies such birth disorders as cerebral palsy. Cerebral palsy is the most common of all birth disorders, affecting about 3 in every 1000 live births in the USA. A loss of blood flow to the developing brain results in ischemic damage to certain brain structures, in particular to the white matter structures around the ventricles. Although a significant amount of research has been performed upon autopsy material and risk factors and patterns of injury have been well characterized, only now are serious attempts being made to investigate the mechanisms that link loss of blood supply in these white matter structures to cell death and loss of brain function.

White matter brain structures are isolated and the cells contained within them are filled with ion-sensitive dyes. Changes in the fluorescent properties of the dyes are then used to quantitate changes in the concentration of various ions within the cells. The cells are exposed to ischemic conditions and increases in ions such as calcium, sodium and hydrogen are monitored. We have found that ischemic injury to the cells is linked to changes in the concentration of these ions, which tend to enter the cells from the extracellular space. One major program therefore involves isolating the pathways through which these ions enter the cells so that appropriate pharmacological means can be found to prevent them from doing so.

This approach allows the cells to be studied within their native structures. That is, the cells are not cultured or otherwise removed from the environment within which they would experience ischemia in the neonatal brain. This philosophy is central to my lab, and we use various other techniques to try to pursue this idea. One major difficulty in the study of cells within their native structures is the identification of cell type. For example, in brain white matter there are at least two kinds of glial cells (astrocytes and oligodendrocytes) in addition to neuronal elements such as axons. We are actively pursuing techniques that allow ion sensitive dyes to be loaded selectively into one or other of these cell types. In this way we can then study the injury process in one type of cell, which is likely to be very different from the injury process in other types of cells.