NHLBI Working Group
Cerebrovascular Biology and Disease
January 28, 2005
The National Heart, Lung, and Blood Institute convened a Working Group
of investigators on January 28, 2005, via conference call to develop a
prioritized list of recommendations for establishing a focused and comprehensive
set of research activities in cerebrovascular biology and disease. The
panel used the National Institute of Neurological Disorders and Stroke's
Report of the Stroke Progress Review Group, published in 2002, as a starting
Our knowledge of cerebrovascular biology and, in particular, the fundamental
mechanisms that regulate cerebral blood flow, is limited. In particular,
the mechanisms by which cerebral blood flow adapts and the cerebral vessel
reacts to environmental insults (such as ischemia, inflammation, trauma,
blood pressure changes, and metabolic stressors) are not well understood.
Significant changes in blood flow or in the integrity of the cerebral
vessel are believed to cause a stroke and contribute to the dementias,
including Alzheimer's disease. New avenues of research need to be developed
that will offer new insights about this vascular bed to lessen the economic
impact and the reduced quality of life caused by stroke and dementia.
These, in turn, will lead to new and better ways to prevent, diagnose,
and treat these disorders.
The expert panel discussed regulation of the cerebral circulation and
the importance of understanding its regulation at the cellular, molecular,
and genetic levels. They developed a strategic plan, beginning with mechanistic
studies, through use of state-of-the art technologies, on the neurovascular
unit, which is involved in regulating microvascular cerebral blood flow.
These studies would continue along a path of increasing biological and
technical complexity and lead toward a more precise understanding of cerebrovascular
biology, development of new drugs, and clinical trials.
Recommendations in three broad areas emerged:
Research on the Neurovascular Unit (NVU):
- Conduct functional genomic and proteomic studies to identify the genes
and their products in the cells comprising the NVU (neurons, glia, and
vascular cells), both in normal and disease states.
- Encourage studies on the embryogenesis and development of the NVU
and on the plasticity induced by functional changes, aging, and disease.
- Investigate the effects of disease and risk factors, including gender
and age, on the NVU and how the function of the NVU is altered, thereby
contributing to stroke or dementia.
- Encourage development of animal models in different species, including
primate models, that reflect human cerebrovascular pathologies (focal
and global ischemia, vascular dementia, low-flow states, etc.)
- Foster development and application of new technologies for studies
of genomic, proteomic, and functional imaging approaches to the NVU.
- Train cerebrovascular pathologists under the auspices of parent research
Cerebrovascular Disease and Translational Approaches:
- Elucidate genotypic and phenotypic characteristics of cerebrovascular
- Use preclinical approaches to develop new therapies based on mechanistic
studies of the NVU.
- Test novel therapeutic approaches in clinical trials in the appropriate
A manuscript will be submitted for publication in a scientific journal.
Stephen S. Goldman, Ph.D., NHLBI, NIH
Working Group Members
Chair: Costantino Iadecola, MD, Department of Neurology &
Neuroscience, Weill Medical College of Cornell University
- David Harder, Ph.D., Medical College of Wisconsin
- Donald Heistad, M.D., University of Iowa
- Zvonimir Katusic, M.D., Ph.D., Mayo Clinic College of Medicine
- Michael Moskowitz, M.D., Massachusetts General Hospital
- J. Marc Simard, M.D., Ph.D., University of Maryland School of Medicine
- Michael A. Sloan, M.D., Rush University Medical Center
- Richard Traystman, Ph.D., Oregon Health and Science University School
Last updated: March 23, 2005