Research Opportunities

We encourage and support residents’ research activities. Opportunities abound at Brown University and Medical School, Rhode Island Hospital, and the other Brown-affiliated hospitals.

The Neurosurgery Research Laboratories offer opportunities for independent or collaborative research. Potential collaborators include faculty researchers and postdoctoral fellows. Typically, about three or four medical students or undergraduates from Brown Medical School are helping with various projects.

Collaborative relationships exist between the neurosurgery department and investigators in neurosurgery, neurology, neuroradiology, neuropathology, and pediatrics. Residents may also team up with other scientists at Brown, such as those in the internationally recognized Department of Neuroscience or the unique Brain Science Program. Key collaborators include Drs. Stopa and de la Monte of Brown’s Department of Pathology and Laboratory Medicine, and John P. Donoghue of the Department of Neuroscience.

Research

The Neurosurgery Research Program

Directed by Conrad Johanson, Ph.D., the Neurosurgery Research Program has earned an international reputation. Its research ranges from basic science to clinical studies and often crosses disciplines.

Most of our experimental work uses rats or mice, including fetal, young adult, aged, and transgenic animals. Whenever possible, we compare information gleaned from animal models and cell cultures with data from specimens of cerebrospinal fluid and human tissue. The program particularly values translational research, the pursuit of knowledge that goes from bench to bedside.

Our research encompasses several areas, including hydrocephalus, Alzheimer’s disease, brain and spinal trauma, ischemia, and brain tumors. The faculty has a special interest in systems that control the interstitial microenvironment of neurons, such as the endothelium of the blood-brain barrier, the epithelium of the choroid plexus, and the ependyma of the CSF-brain interface.

Hydrocephalus

Neurosurgery Program scientists are investigating congenital hydrocephalus, a disease of childhood; normal pressure hydrocephalus, an increasingly prevalent condition in geriatric patients; and intracranial benign hypertension, which mainly afflicts women. Congenital hydrocephalus usually requires shunting of the excess cerebrospinal fluid (CSF), but shunts can become infected and necessitate further surgery. To overcome this problem, our researchers are trying to identify factors, such as peptides, that promote CSF reabsorption. They hope to find drug alternatives to shunts.

In normal pressure hydrocephalus, the ventricles expand without a substantial rise in intracranial pressure. This type of hydrocephalus often accompanies Alzheimer’s disease. Collaborative research, with Gerald Silverberg, M.D., of Stanford University and the Eunoe Corporation, is evaluating transport mechanisms that remove amyloid protein from the brain extracellular fluids. This basic research is prompted by encouraging clinical findings suggesting that shunting of some Alzheimer’s patients improves cerebral function.

Alzheimer’s Disease

Alzheimer’s disease is not typically considered a neurosurgical problem; however, interest is growing in the notion that disturbed CSF dynamics may contribute to the impairment seen in Alzheimer’s patients. In fact, draining off the excess CSF may improve the cognitive functioning of some patients.

Much of our research on Alzheimer’s disease focuses on pathology of the endothelium of the blood-brain barrier and the epithelium of the choroid plexus. Disruption of these barriers may exacerbate neurodegeneration. Consequently, we are using a mouse model to determine whether changes in growth factors and their receptors alter the development of Alzheimer’s-like pathology.

Trauma of the Brain or Spinal Cord

Neurosurgery Program researchers are investigating how the brain and spinal cord respond to injury. The dogma that adults cannot grow new neuronal connections has yielded to the recognition of growth factors and their part in healing the central nervous system (CNS).

Much of our research on trauma involves animal models. For instance, we study spinal injury by clamping a rat’s spinal cord and observing how the CNS reacts. Similarly, a rodent model of controlled cortical impact simulates traumatic injury to human brains.

Recovery from traumatic brain or spinal cord injuries is often complicated by cerebral edema, which increases the risk of death. To gain a thorough understanding of the molecular and cellular mechanisms underlying edema formation in the CNS, we augment animal studies with the analysis of cell culture models. These investigations focus on the potential role of neuropeptides, growth factors, and inflammatory cytokines in controlling the brain environment and the integrity of brain barriers. Their results are likely to reveal new molecular targets that could lead to better treatments for cerebral edema.

Ischemia

Our stroke research focuses on transient forebrain ischemia or acute stroke. Using microsurgical techniques, we surgically isolate and clamp rats’ carotid arteries to produce ischemia. Findings from the neurosurgery laboratories indicate that the choroid plexus, via the CSF, supplies the brain with neuroprotective factors that facilitate recovery from ischemic injury. Analyzing interactions between the hippocampus and the adjacent choroid plexus has shed light on the memory problems that humans face after acute ischemic stroke.

Brain Tumors

Neurosurgery Program researchers are engaged in both basic and clinical research on malignant brain tumors. Our basic science work concerns immunotherapy and gene therapy for malignant brain tumors. We are also conducting clinical trials of potential new treatments for these tumors.

In collaboration with the Division of Pathology, we established an in vivo rat glioblastoma model to study surgical and gene therapy. Our research shows that implanting glial tumor cells into rats improves their response to chemotherapy. A similar approach may prove to be a useful adjunct to chemotherapy in humans. The next steps include finding the best means of delivering the therapeutic agent and identifying ways to use immuno-gene therapy to induce tumor rejection.

Department of Neuroscience

The Department of Neuroscience, led by chairman John P. Donoghue, Ph.D., is devoted to the scientific study of the nervous system from the level of molecules to behavior. Its investigators use a variety of methods to discern how the brain works, including in vivo and in vitro techniques, functional magnetic resonance imaging, and mathematical modeling. Areas of inquiry directly relevant to clinicians include experimental neurosurgical methods, neural prosthetics, brain plasticity, epilepsy, and cortical circuits.

Brain Science Program

Brown University’s Brain Science Program fosters a collaborative, multidisciplinary approach to understanding brain function through research and education. Directed by John P. Donoghue, Ph.D., and Nobel prizewinning physicist Leon Cooper, Ph.D., the program brings together more than 100 faculty members from fields as diverse as Cognitive and Linguistic Sciences, Computer Science, Neuroscience, Psychology, Physics, Psychiatry, Clinical Neuroscience, Applied Mathematics, Biology and Medicine, and Engineering.

The program’s research addresses the following questions:

  • How do we interact with the world?
  • How do we fix the damaged brain?
  • What neural codes does the brain use to represent information?
  • How do we learn and remember?
  • How do we see and recognize objects?

Research Facilities and Equipment

The Neurosurgery Research Laboratories

The Neurosurgery Research Laboratories occupy two floors of the Aldrich Research Building on the Rhode Island Hospital campus. They include the Molecular Biology Laboratories, facilities for cell culture and microscopy, and space for conducting pathophysiological research on animals. The laboratories contain:

  • a microtome,
  • a Kodak Image Station,
  • a real-time polymerase chain reaction machine,
  • -70°C freezers,
  • cell incubators, and
  • photography hardware and software.

The Central Animal Facility

The Central Animal Facility, in a building adjacent to Aldrich, contains surgical laboratories for microsurgery, electrophysiology, and special radiographic procedures. It houses two operating rooms and X-ray angiography suites. Veterinarians are available in the AAALAC-acccredited animal-care program.

The Core Research Laboratories

The Division of Core Research Laboratories, directed by Paul N. McMillan, Ph.D., provides technical services to the research community. The laboratories offer:

  • digital imaging, image analysis including stereo morphometry, and confocal microscopy
  • flow cytometry with cell-sorting capability
  • DNA sequence analysis
  • gel scan analysis
  • histology and histochemistry
  • transmission electron microscopy
  • scanning electron microscopy with X-ray microanalysis capability

The Neuropathology Laboratories

The Neuropathology Laboratories in the Aldrich building contain all of the equipment needed for conducting polymerase chain reactions, in-situ hybridrization, Western blots, and ELISA assays. Several paraffin and cryomicrotomes are available for performing a wide range of histological techniques, as well as an LKB model PMV cryomicrotome, designed to cut full coronal and transverse frozen sections of the whole brain.

Other equipment in the Neuropathology Laboratories includes tissue culture facilities, hybridization ovens, a Leitz microscope, and a laser-capture dissecting microscope. The laboratories also contain a three-headed Olympus microscope with photographic accessories and image-analysis capabilities.

The Brown Brain Bank obtains human brain tissues from a large geographic area that covers nearly all of southeastern New England. Most of the approximately 400 brains have come from patients with Alzheimer’s disease; about a fifth are from normal controls. The bank supplies tissues to investigators at Brown and around the world.

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