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.
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
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
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.
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
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.
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.
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
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.