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Brain's blood supply guides its own
development
MGH-led study finds vascular
development guided by intrinsic factors, not neuronal needs
BOSTON - March 16, 2008 - A new study from investigators
at Massachusetts General Hospital (MGH) paints a radically different
picture of how the brain's blood supply develops. Their report in
the journal Nature Neuroscience, which has received early
online release, describes how blood vessels in the brain grow according
to their own agenda beginning early in fetal life and finds that
the vasculature of embryonic brain may actually guide later development
of brain cells and their connections.
"Until now it was believed that, as our brains grew and as
neuronal connections and nerve fibers formed, blood vessels carrying
oxygen and other nutrients grew passively to meet the brain's metabolic
needs," says Pradeep
Bhide, PhD, director of Research for MGH Neurology and senior
author of the paper. "This new study calls for a complete revision
of that model of brain vascular development and places emphasis
on genetic mechanisms guiding the proliferation and migration of
the cells that make up blood vessels."
It is common knowledge that the brain receives the lion's share
of the blood supply and that even brief interruption of cerebral
bloodflow can result in stroke and permanent brain damage. The anatomy
of the brain's vascular networks is as complex and fascinating as
neuronal networks, but surprisingly little has been known about
how the lifelong close relationship between blood vessels and brain
cells develops.
To investigate this question, the MGH scientists and their collaborators
labeled endothelial cells, building blocks of blood vessels, with
fluorescent markers and followed their complex behaviors and migrations
as they maneuvered to build tiny new blood vessels in fetal brains
of mice. They found that the cells divided and migrated and new
blood vessel assembly occurred in a highly coordinated and orderly
fashion. Transgenic mouse models confirmed that the endothelial
cells were responding to their own genetic programs - not those
governing the formation of neurons - and not merely reacting to
the growing metabolic demands of brain tissue.
"In addition, we found that some of the genes that regulate
neuronal development also regulate endothelial cell development,
which unifies the principles of development of both cell types.
Our study also finds that endothelial cells in the fetal brain may
guide development of neuronal networks and places the embryonic
brain's vasculature in a position to play dual and independent roles
of supplying nutrition and carrying instructive signals for brain
development," says Bhide, who is also director of the MGH
Neuroscience Center and an associate professor of Neurology
at Harvard Medical School. He and his colleagues anticipate that
insights emerging from this study could improve understanding of
brain malformations and developmental disorders by shifting focus
towards mechanisms regulating development of blood vessels in the
fetal brain.
Anju Vasudevan, PhD, of the MGH Neuroscience Center is the lead
author of the Nature Neuroscience article. Study co-authors
are Jason Long, PhD, and John Rubenstein, MD, PhD, University of
California at San Francisco; and James Crandall, PhD, University
of Massachusetts Medical School. The study was supported by grants
from the National Institutes of Health.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
Media Contacts: Emily
Parker , MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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