As part of the Department of Neurological Surgery’s mission to improve the lives of patients through research and development, the Walter L. Copeland Laboratory suite was dedicated in November 1999 to serve as the core facility for neurosurgical basic science research. This 3,800 square foot facility, located on the ninth floor of Scaife Hall houses several research disciplines within the department including neuro-oncology, radiation biology and therapy, neurophysiology, neurotrauma and resident training. In addition, the laboratory suite provides core services in the areas of molecular biology, biochemistry, histology and immunohistochemistry. It is through the ongoing research within the Copeland laboratory that the therapies of tomorrow are being developed and tested.

Innovative research in the area of brain tumor therapies include the use of immunologic agents, the study of tumor angiogenesis, and the use of neural stem cells in order to treat brain tumors and minimize morbidity. In immunotherapy approaches to brain tumor destruction, there currently exists a trade off in terms of targeting tumor antigens without killing normal brain tissue. Possible adverse events in immunotherapy may include the induction of an auto immune response against normal brain tissue. Current research studies in the laboratory utilize dendritic cells to enhance the activity of therapeutic immunity and to prevent the destruction of normal brain tissue.

Another strategy in brain tumor research is to target the blood supply to an existing tumor so as to deprive the tumor specifically of nutrients necessary for survival. Initial studies are under way to unravel gene expression changes that occur within the microvascular endothelial cells in response to growth signals from malignant brain tumors. Potentially, interference of these signals would help to limit the growth of tumors. Through the use of Serial Analysis of Gene Expression (SAGE), a powerful tool for analyzing gene expression changes associated with neoplasia, several genes that are selectively expressed in glioma endothelium have been identified.

Still another part of the brain tumor therapy focus is on how to improve therapy for brain tumors while minimizing damage to the surrounding normal tissue. To enhance tumor killing, genetically-engineered neural stem cells that can be transplanted into brain tumors as vehicles for the delivery of therapeutic agents have been designed and are being tested for future clinical trials.

Radiation has long been an effective method for controlling and treating cancer and in particular brain tumors. Unfortunately, radiation injury to surrounding tissue can lead to extensive and diffuse damage which can lead to neurologic morbidity. An active research program within the Copeland laboratories is looking for ways to limit or prevent damage to a normal brain as a result of radiation therapy. For reasons that are presently unknown, the child’s brain appears to be particularly sensitive to irradiation. Brain irradiation of children, used in the treatment of primary brain tumors and as a preventative measure against metastatic disease, can have severe side effects and result in significant learning disabilities. By establishing the mechanisms of radiation-induced cognitive deficits and, then developing strategies to decrease the incidence and severity of brain injury in children following radiation therapy, researchers hope to improve the potential use of radiation therapy in children with brain tumors and limit the long term impact.

The research activity of the Neurophysiology Research Group has been particularly active with the development of biomedical sensors and electronic circuits, as well as high precision mechanical processing in support of these developments. Major developments include a 300 channel automatic EEG electrode placement system, a new skin screw EEG electrode which requires no skin preparation, and a volume conduction based implantable data communication device that transmits signals between the inside and outside of the human body. Recent work in the area of energy metabolism and neurophysiology technology is attempting to harvest energy from the human body by converting glucose from within the body fluid into electricity in order to power implantable devices such as those implanted within the brain for the treatment of Parkinson disease and epilepsy. In this way, battery life or device failures could be minimized.

Another area of new interest has been in the area of traumatic brain injury in children. Traumatic brain injury remains the leading cause of death and disability in children affecting over 150,000 children each year. Many of these children, even those with mild concussions frequently suffer long-term or permanent disabilities. The research group in pediatric neurotrauma at the Copeland Laboratory has focused on the acute care of children immediately following a severe injury and includes the use of hypothermia or cooling as a means to reduce secondary injury and improve outcome. Because of its history, this basic laboratory work will directly lead to a translation to clinical research. The goal of the research efforts is to not only understand the pathophysiologic response of the immature brain to injury but also to develop novel therapeutic treatments to lessen brain injury and improve long term function in these children. This model of translational research underscores the efforts in the Copeland Laboratory and future clinical trials to be directed by the department faculty.

In addition to the basic translational research within the facility, the Copeland Laboratory suite is also a central location for core services. As an essential part of resident training, department faculty members instruct resident training courses in surgical technology and hands on techniques utilizing cadaver dissection and microvascular surgery in preparation for work in the clinical arena. Training courses are given throughout the year and are conducted in a laboratory equipped with five dissecting microscopes and a video monitoring system. The Copeland Laboratory provides a full range of histologic services that include the preparation of histologic slides from frozen or paraffin-embedded tissue, routine staining techniques, and immunohistochemistry.

The basis of the mission of the Department of Neurological Surgery is to improve the lives and care of our neurosurgical patients. Integral to this is research into the basic science of neurosurgical disease and treatment. The Copeland Laboratories serves to provide a state-of-the-art setting where collaborative innovative research takes place.