Research Opportunities

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Studies are underway in the Department of Neurological Surgery in the following areas:

Neurophysiology

Many studies focus on the basic mechanisms underlying epileptiform activities. The in vitro slice preparation is used to examine tissue from animal models and from human epileptic foci resected at surgery. In a separate, but related line of investigation, we are studying the development of mammalian CNS, particularly the hippocampus, with electrophysiological, pharmacological, immunocytochemical, and electron microscopic tools. Local circuitry connections and characteristics of interneuron populations supplement these studies. A major topic of investigation is plasticity in the central nervous system, manifested by such phenomena as long-term potentiation of synaptic transmission, changes associated with brain lesions, and brain repair by transplantation techniques. A major effort is underway to understand glial influences on neuronal plasticity, firing properties and repair mechanisms. This is achieved by electrophysiological and morphologic techniques.

Central Nervous System Oncology

There are multiple areas of activity in neuro-oncology:

One major area of laboratory research in neuro-oncology is concerned with defining the relationship between aberrations in growth factors and growth factor receptor expression and glioma development and progression. The fibroblast growth factor (FGF) family of mitogens and receptors is being actively studied in normal brain and in malignant brain tissues.

Another major area of research interest is focused on malignant brain tumor migration invasion. Utilizing both in vitro and in vivo models as well as human tissue obtained from surgical procedures in the operating room, factors that affect motility invasion and that alter these processes are under investigation. Quantification of the resolution of imaging studies and the impact of therapies on these invading brain tumor cells are also under investigation.

A third focus of research in neuro-oncology involves delineating the role that transcription factors, that normally regulate CNS progenitor cell development, play in CNS tumors. Studies include analyzing the molecular biology of skull base tumors (meningioma, schwannoma, chordoma etc.) as a preliminary step in devising better treatment strategies, such as gene therapy, for patients with unresectable or maximally radiated tumors.

A fourth area of research in neuro-oncology is directed toward defining the genomics and molecular biology of malignant glial cells. An extensive central nervous system tumor cell library includes adult and pediatric brain tumors, and is available for research investigations. One such example is the development of cell lines resistant and sensitive to standard chemotherapeutic agents, and defining the mechanisms of drug resistance in malignant glial cells, and developing ways to overcome these resistant pathways. Another area focuses on the glial cell and tumor cell motility and invasiveness of malignant cells.

Additional efforts with other laboratories include brain tumor metabolism studies using PET scan, overcoming bone marrow toxicity to chemotherapy agents (Fred Hutchinson Cancer Research Center), and radiobiology research with hypoxic cell sensitizers. Interstitial brachytherapy is an integral part of this diverse neuro-oncology program.

Clinical research interests include research protocols for the treatment of malignant brain tumors, including novel chemotherapeutic treatments and implantation of chemotherapy and radiation in resection cavity of malignant tumors.

Cerebral Ischemia and Neuroprotection Research

This laboratory is involved in studying mechanisms of ischemic neuronal damage and the effects of neuroprotective compounds. The laboratory utilizes hippocampal slice cultures which are slices from rat brain which are maintained in a tissue culture environment. Neuronal insults such as ischemia, anoxia, or direct administration of neurotoxins, are used to cause selective neuronal damage and neuroprotective compounds are evaluated. Biochemical pathways leading to ischemic neuronal damage are also active areas of investigation.

Cerebrovascular and Vascular Smooth Muscle Physiology

Studies are being carried out evaluating the regulatory mechanisms of cerebral blood flow and metabolism, using various techniques for measuring cerebral blood flow as well as analytical neurochemical techniques for measuring brain metabolites. The ability to isolate 20-40 micron cortical vessels from animals is ongoing, and the biophysics and neurochemistry of these regulatory vessels is presently being determined, with special attention to adenosine as a regulator of cerebral blood flow. Other studies involve the use of in situ pial windows, cell culture, and electrophysiologic techniques, as well as morphologic assessment of arterial vasospasm after subarachnoid hemorrhage and endothelial injury to systemic arteries.

Neuroanatomic Studies

These include Golgi electron microscopy techniques and degeneration studies of experimental epileptic foci and epileptic foci excised from patients, as well as fundamental studies of synaptic contacts in cortex and brain stem, their development, and their neuroplastic modification by discrete lesions. Transport techniques are used to study normal, developing, and experimentally altered cortical and brain stem pathways. Light and electron microscopic immunocytochemistry of neurotransmitters and receptor binding of receptor ligands are being studied in cortex and brain stem to evaluate normal distribution and changes with maturation and during neuroplastic reorganization. Anatomical details of the central effects of peripheral nerve lesions are also under investigation, as are morphologic techniques to demonstrate central sites of representation for peripheral nerves and structures.

Behavioral Physiology

Studies in departmental laboratories have included evaluations of the effect of experimental interventions, various drugs, and sub-cortical lesions. The facilities of the Regional Primate Center are available for primate studies.

Cortical Localization

The effects of stimulation of cerebral cortex and of various subcortical structures on speech and visuo-spatial short-term memory functions are being studied in patients undergoing stereotaxic operations, tumor resection and cortical excisions for epilepsy, pain and movement disorders.

Epilepsy

The Regional Epilepsy Center is an eight bed unit, located at Harborview Medical Center which has the capacity for 24 hour monitoring and is staffed by neurologists and several neuropsychologists. A similar facility is based at Children's Hospital & Regional Medical Center. Both medical and surgical evaluation and treatment of epilepsy are being investigated. A variety of clinical research projects are ongoing in these centers.

Investigations are also ongoing with regards to the use of vagal nerve stimulators for control of generalized seizures, intraoperative mapping of cortex for studies on language and memory, and intraoperative microelectrode recordings of individual neurons for further studies on the origins of epilepsy.

Pain

The Department is intimately involved in the activities of the Pain Clinic. A large interdisciplinary group is studying basic and clinical mechanisms relating to pain.

Stereotaxic Localization of Human Brain

Theodore Roberts, M.D., developer of the Brown-Roberts-Wells frame, leads investigations to further define and extend the use of stereotactic localization in human brain.

Skull Base Clinical Research

In cooperation with the Department of Otolaryngology/Head & Neck Surgery and Bloedell Hearing Center, the Neurological Surgery Department has an active research program in diseases and surgery of the skull base. Opportunities exist for basic and clinical training and research in a wide spectrum of laboratories. In addition, there is a "hands on" skull base laboratory for residents to gain familiarity with these complex procedures and anatomy.

Cerebrovascular Laboratory

The cerebrovascular (TCD) laboratory provides services for all four hospitals. This laboratory is a state of the art facility which has ongoing clinical research focused on the physiology and pathophysiology of the cerebral vasculature. Rune Aaslid, the developer of the TCD technique is a member of our faculty.

Trauma of the Central Nervous System

Clinical and basic science research activities are focused on trauma of the central nervous system. Clinical efforts include a study of anti-epileptic medication and magnesium in the treatment of post-traumatic epilepsy, use of methylprednisolone in spinal cord injury, lasaroid intervention in treatment of traumatic brain injury, as well as the maintenance of a comprehensive patient data base.

A basic science laboratory is dedicated to trauma of the central nervous system using experimental brain injury models in rodents. This laboratory focuses on neuroanatomic changes after brain injury, particularly those neuronal systems involved in memory, as well as changes at the cellular level with particular focus on glial cells.

Peripheral Nerves and Spinal Cord

Improvements in the diagnosis and surgical/medical treatment of peripheral nerve disorders are being pioneered at the University of Washington, employing high resolution magnetic resonance imaging (MRI) techniques and electrophysiological studies (e.g. EMG, nerve conduction). Clinical trials are currently in progress using new methods to reduce scar formation following surgery. In addition, an active laboratory research program directed by Michel Kliot, M.D. is aimed at understanding the biology of peripheral nerve injury and recovery that complements clinical practice.

Pediatric Neurosurgery

Areas of research include the pathophysiology of hydrocephalus, craniofacial disorders, spinal dysraphism, and pediatric neuro-oncology.

Academics : Research Opportunities | Awards | Resources

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