Bone marrow, the spongy tissue inside most of our bones, produces red blood
cells as well as immune cells that help fight off infections and heal injuries.
According to a new study of mice and humans, tiny tunnels run from skull bone
marrow to the lining of the brain and may provide a direct route for immune
cells responding to injuries caused by stroke and other brain disorders. The
study was funded in part by the National Institutes of Health and published
in Nature
Neuroscience.
“We always thought that immune cells from our arms and legs traveled via
blood to damaged brain tissue. These findings suggest that immune cells may
instead be taking a shortcut to rapidly arrive at areas of inflammation,” said
Francesca Bosetti, Ph.D., program director at the NIH’s National Institute of
Neurological Disorders and Stroke (NINDS), which provided funding for the
study. “Inflammation plays a critical role in many brain disorders and it is
possible that the newly described channels may be important in a number of
conditions. The discovery of these channels opens up many new avenues of
research.”
Using state-of-the-art tools and cell-specific dyes in mice, Matthias
Nahrendorf, M.D., Ph.D., professor at Harvard Medical School and Massachusetts
General Hospital in Boston, and his colleagues were able to distinguish whether
immune cells traveling to brain tissue damaged by stroke or meningitis, came
from bone marrow in the skull or the tibia, a large legbone. In this study, the
researchers focused on neutrophils, a particular type of immune cell, which are
among the first to arrive at an injury site.
Results in mouse brains showed that during stroke, the skull is more likely
to supply neutrophils to the injured tissue than the tibia. In contrast,
following a heart attack, the skull and tibia provided similar numbers of
neutrophils to the heart, which is far from both of those areas.
Dr. Nahrendorf’s group also observed that six hours after stroke, there
were fewer neutrophils in the skull bone marrow than in the tibia bone marrow,
suggesting that the skull marrow released many more cells to the injury site.
These findings indicate that bone marrow throughout the body does not uniformly
contribute immune cells to help injured or infected tissue and suggests that
the injured brain and skull bone marrow may “communicate” in some way that
results in a direct response from adjacent leukocytes.
Dr. Nahrendorf’s team found that differences in bone marrow activity during
inflammation may be determined by stromal cell-derived factor-1 (SDF-1), a
molecule that keeps immune cells in the bone marrow. When levels of SDF-1
decrease, neutrophils are released from marrow. The researchers observed levels
of SDF-1 decreasing six hours after stroke, but only in the skull marrow, and
not in the tibia. The results suggest that the decrease in levels of SDF-1 may
be a response to local tissue damage and alert and mobilize only the bone
marrow that is closest to the site of inflammation.
Next, Dr. Nahrendorf and his colleagues wanted to see how the neutrophils
were arriving at the injured tissue.
“We started examining the skull very carefully, looking at it from all
angles, trying to figure out how neutrophils are getting to the brain,” said
Dr. Nahrendorf. “Unexpectedly, we discovered tiny channels that connected the
marrow directly with the outer lining of the brain.”
With the help of advanced imaging techniques, the researchers watched
neutrophils moving through the channels. Blood normally flowed through the channels
from the skull’s interior to the bone marrow, but after a stroke, neutrophils
were seen moving in the opposite direction to get to damaged tissue.
Dr. Nahrendorf’s team detected the channels throughout the skull as well as
in the tibia, which led them to search for similar features in the human skull.
Detailed imaging of human skull samples obtained from surgery uncovered the
presence of the channels. The channels in the human skull were five times
larger in diameter compared to those found in mice. In human and mouse skulls,
the channels were found in the both in the inner and outer layers of bone.
Future research will seek to identify the other types of cells that travel
through the newly discovered tunnels and the role these structures play in health
and disease.
Source:
https://www.nih.gov/news-events/news-releases/researchers-unearth-secret-tunnels-between-skull-brain
https://www.nih.gov/news-events/news-releases/researchers-unearth-secret-tunnels-between-skull-brain
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