Researchers in the Division of Neurology and their collaborators in other divisions at Children's Memorial and at other universities across the U.S. conduct epidemiological, translational, and basic laboratory research targeting a wide range of conditions that cause injury or death of brain cells (neurons). The objective of this research is to find new therapies to prevent neural tissue injury. This field is often referred to as "neuroprotection."

Leon Epstein, MD, has led a group of researchers for nearly 15 years who have studied the pathways by which viruses such as HIV (the AIDS virus) cause inflammation in the brain. This activation of special inflammatory cells (called microglia) in the brain results in the release of substances called cytokines. While these naturally occurring substances can be helpful in fighting infections they can also cause neurons to become overly excited and die (referred to as excitotoxicity).

These same pathways have been implicated in many other conditions including stroke, hypoxic injury (insufficient oxygen) in the newborn, the complications of organ transplantation and the adverse effects of chemotherapy for brain and other cancers. Ongoing drug development funded by the NIH (National Institutes of Health) and directed by Dr. Epstein is specifically searching for treatments for HIV-induced neuronal injury, however, these treatments could have broad applicability to all of the conditions above. Promising compounds discovered in the laboratory have been brought to clinical trials (translational research). The object of this research is to find new therapies to prevent neural tissue injury.

Mark Wainwright, MD, PhD, recently joined the division from Duke University. Dr. Wainwright's interest is neuroprotection from hypoxic brain injury in newborns. Dr. Wainwright is investigating a number of strategies including medications and hypothermia in this setting. Similarly, Dr. Kent Kelley, of the Children's Epilepsy Center, is especially interested in seizures in the newborn period. Monitoring newborn infants with severe seizures has taught us that conventional anticonvulsant medications are not sufficient to stop seizures and prevent excitoxitic injury to brain cells. This is yet another opportunity to prevent injury at a critical time when the baby's nervous system is still developing.

Research in neuroprotection is essential if we are to improve the long term outcomes and quality of life of children with neurologic disorders.

Dr. Jeffrey Nye is interested in how genes control development of the brain and how these genes contribute to neurological disease. A major effort in his lab is aimed toward understanding the Notch pathway, specifically, its roles in neurogenesis, the pathogenesis of presenilin-linked Alzheimer's disease and its mechanism of signal transduction. These studies are performed in developing embryos from transgenic or mutant mice, as well as cell culture and biochemical systems. A second major effort concerns the genetic basis of neural tube defects, commonly called spina bifida, looking for mutations in genes that control neural development in patients with spina bifida.