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Basic & Clinical Research Activities

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This is our main Research@Neurosurgery web site for research related information. It hosts summaries of information on both Clinical and Basic Science research activities that are being conducted by members of the Neurological Service at MGH.

Information about programs, projects, and laboratories in Neurosurgery that conduct Basic Science Research and Clinical Research can be found under either the name of the individual Principal Investigators or under their Laboratories. Links to the research areas are always available on the left of your screen.

Please note: the information is indexed by type of research, but many of the Neurosurgical Service Faculty conduct both Clinical and Basic Science research programs.

The clinical faculty, most of whom have a significant research interest, are joined in the department by basic researchers covering a broad spectrum of neurobiology, neurophysiology, and neuropathology. Neurosurgery Residents develop research projects in conjunction with the Neurosurgery research faculty, in collaboration with other MGH departments and throughout Harvard community.

The Center for Nervous System Repair headed by Dr. Jeffrey Macklis, Director offers exciting new opportunities. “We are focused in the general fields of CNS repair, neural precursor / “stem cell” biology, and adult neurogenesis. We are working toward the cellular repair of cerebral cortex output neuron circuitry lost in neurodegenerative diseases and damaged by spinal cord injury (in particular, corticospinal motor neurons and the corticospinal tract). We are especially focused toward induction of adult neurogenesis; elucidating the molecular controls over the development of corticospinal motor neurons and other important lineages of cortical projection neurons; directed differentiation of replace ment neurons; and functional integration of replacement neurons derived from adult neural precursors, also called “adult neural stem cells.
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Types of Research Activities

Within the Department of Neurosurgery itself, the research activities can be grouped in 5 major areas:
  • Brain Tumors
  • Neural Growth and Regeneration
  • Intraoperative Monitoring and Imaging
  • Cerebral Blood Vessels
  • Cellular Neurobiology
  • Neurophysiology
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Brain Tumors

The natural history of brain tumors is being studied in collaboration with the Department of Pathology. This work focuses on the mutation or series of mutations that occur in glioblastomas. This work concentrates on the use of PPCR methodologies to amplify the DNA of biopsy specimens and of archival neuropathology slides. The latter are particularly useful since the outcome is known. A series of mutations have been found to occur in naturally occurring brain tumors. Many tumors have a mutation of the p53 gene. Another common mutation is amplification of the EGFR (epidermal growth factor receptor) gene.

A second area of brain tumor research is the use of retroviral therapy against glioblastomas. The goal is to use retroviruses to introduce into the tumors genes that would either kill the tumor cells, later their pattern of growth, or sensitize them to chemotherapeutic agents. One such trial involves the introduction of a gene for thymidine kinase. A number of analogous manipulations are being tested both vitro and in rats.
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Neural Growth and Regeneration

A major long-term goal for Neurosurgery is the restoration of damage of function that has been lost due to damage to the nervous system. Two research areas aim toward that goal.

Work carried out in collaboration with the Department of Neurology involves the attempt to implant cultured neurons into the brains of animals following experimentally induced brain damage. The basal ganglia are the focus of this work and dopamine-releasing neurons are being implanted into the brain following experimental lesions of the dopamine-containing brain neurons. Similar strategies can be applied to other brain models.

On the more fundamental level, we are trying to learn the factors that promote the growth of neurons. This is being carried out using cultured cells. A new factor released by immortalized cultured glia has been discovered. It promotes a neurite outgrowth from a variety of projection neurons. Current studies are aimed at identifying and cloning the factor.
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Intraoperative Monitoring and Imaging

A major area of clinical research concerns surgery for epilepsy. Candidates for epilepsy surgery are intensively studied by electrophysiological and imaging techniques. Electrophysiologically, implanted electrodes are used to monitor seizure activity in awake patients. PET imaging is used to localize motor and language areas. New technology allows superimposition of the PET images with MRI scans, providing sharply defined landmarks during surgery. A further area of exploration is the use of virtual imaging in the operating room.

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Cerebral Blood Vessels

Blood vessels are being studied from several perspectives. A major research program concerns the biology of cerebral stroke. Research in this area includes studies on imaging of cerebral blood flow with a variety of modern imaging techniques. A basic laboratory program studies in vitro systems toward the goal of learning what might protect nervous tissue from interruptions of its supply of glucose and oxygen. Neuroprotective agents such as cooling and neurotransmitter antagonists are currently under study. In addition, laboratory studies aimed at extending the in vitro studies to the in vivo situation are carried out. Commonly ischemia is caused in a neural region, and agents that might reduce the severity of the infarct are tested. These studies have led to introduction of certain therapeutic maneuvers in the operating room, notably mild cooling in patients whose cerebral circulation must be interrupted for surgical reasons.

A major research area concerns the biology of headache. In the laboratory, the innervation of the blood vessels has been intensively studied. The sequence of events attending migraine have been delineated
using extravasation of tracers as a marker. A new series of anti-migraine drugs is being developed and tested both in vitro and in vivo.

A major laboratory studies cerebral vasospasm. In the laboratory, isolated dog arteries are perfused in vitro and the factors that constrict and relax them are studied. In vivo, vasospasm may be experimentally induced in dogs by subarachnoid injection of blood. This provides a model in which to test potential maneuvers aimed at reducing the spasm. Recently, a major collaboration with the MGH Laser Laboratories has resulted in a potential new therapeutic invention. High intensity laser pulses are applied at the site of spasm. In dogs, these succeed in relaxing the vessel. Phase 1 trials of this intervention are being planned.
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Cellular Neurobiology

Within the Department of Neurosurgery there are also laboratories of fundamental neurobiology. These are concerned with various aspects of neuroanatomy and neurophysiology.

One area of focus is the cell biology of the retina. The retina is used as a model system for studies of how small neural networks operate computationally upon their inputs. This laboratory uses anatomical methods and combined anatomy/physiology studies of in vitro retinas.

Another area of research concerns the biology of membrane proteins, particularly the Na,K-ATPase. These studies are aimed at understanding the heterogeneity of the Na,K-ATPases in the brain and their regulation.

 
 
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