Cerebrovascular Biology and Disease

Discussion:

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:

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.

Resource Development:

• 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 grants.

Cerebrovascular Disease and Translational Approaches:

• Elucidate genotypic and phenotypic characteristics of cerebrovascular diseases.
• Use preclinical approaches to develop new therapies based on mechanistic studies of the NVU.
• Test novel therapeutic approaches in clinical trials in the appropriate patient populations.

Publication Plans:

A manuscript will be submitted for publication in a scientific journal.

NHLBI Contact:

Stephen S. Goldman, Ph.D., NHLBI, NIH
goldmans@mail.nih.gov

Working Group Members

Chair: 

• Costantino Iadecola, MD, Department of Neurology & Neuroscience, Weill Medical College of Cornell University

Members:

• 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 of Medicine