Infection hinders blood vessel repair following traumatic brain or cerebrovascular injuries
Study in mice demonstrates the importance of quickly addressing infection


Date:
September 23, 2021
Source:
NIH/National Institute of Neurological Disorders and Stroke
Summary:
Traumatic brain injury (TBI) and other injuries to blood vessels in
the brain, like stroke, are a leading cause of long-term disability
or death.

Researchers have found a possible explanation for why some patients
recover much more poorly from brain injury if they later become
infected.



FULL STORY ========================================================================== Traumatic brain injury (TBI) and other injuries to blood vessels in
the brain, like stroke, are a leading cause of long-term disability or
death. Researchers at the National Institute of Neurological Disorders
and Stroke (NINDS), part of the National Institutes of Health, have
found a possible explanation for why some patients recover much more
poorly from brain injury if they later become infected. The findings
were published inNature Immunology.


========================================================================== Making use of a mouse model for mild TBI (mTBI) that they had developed previously, the team of researchers led by NINDS scientist Dorian
McGavern, Ph.D., discovered that viral, fungal, or a mimic for bacterial infections all impacted blood vessel repair within the meninges,
the protective covering of the brain. When they looked closer, they
observed that some cells of the immune system no longer moved into the
site of the injury, which occurred in the uninfected animals, suggesting
they were responding to systemic infection. The study also looked in a
second injury model affecting the blood vessels in the brain, called a cerebrovascular injury (CVI), and saw a similar effect on repair.

"Evolution prioritizes mobilizing the immune system to fight off infection
over repair," said Dr. McGavern. "Because the body is dealing with a
greater threat, cells that would normally repair the damaged blood vessels
in or around the brain are needed elsewhere." This change in priority
for the immune system is not permanent, as infected mice were able to eventually repair the blood vessel damage at a later time compared to uninfected mice, unless a second infection was encountered. This timing
is especially critical in the case of CVI mice, because the delay in
response produced by infection led to permanent cognitive dysfunction
and damage to the brain tissue. The repaired brain blood vessels, which
are normally very well sealed, remained permanently leaky.

"The presence of infection causes the immune system to take a break from
repair while it fights off the virus," said Dr. McGavern. "In the case
of mild TBI, this seems to be ok, but when you have a large vascular
injury in the brain itself, like a stroke, every minute counts. These
findings highlight the utmost importance in quickly identifying and
treating infections in patients." Although the presence of infection
was affecting the immune system's ability to respond to mTBI, the exact
cause remained unknown. When cells in the body become infected, they
call for help by releasing proteins that signal the immune system. One
group of proteins released after viral infection are called type I
interferons (IFN-I), which turn on a variety of genes that affect the
immune response. Following mTBI, the researchers saw a large increase
in IFN-I- related genes in infected compared to non-infected mice.

Additional experiments confirmed the importance of IFN-I in shifting
the focus of the immune system away from blood vessel repair. Mice that
have had their genome altered so that their immune cells cannot sense the presence of IFN- 1 showed similar rates of repair after mTBI regardless
of whether they had a viral infection. Deleting the IFN-I sensor only in
one type of immune cell known to be important for repairing blood vessels
after mTBI also eliminated the defect produced by infection. Finally,
directly applying one of the IFN- I proteins directly to the injury site prevented blood vessel repair without the presence of infection. IFN-I signaling also appeared to play a critical role in the repair delay seen
in CVI mice.

Systemic infections are common among patients hospitalized for TBI
and CVI, and they have been linked to poorer outcomes. The findings
in this study highlight the importance of controlling those infections
(whether bacterial or viral) as quickly as possible. This is especially
true for CVI patients, as a delay in repair can lead to permanent damage
to the brain.

========================================================================== Story Source: Materials provided by NIH/National_Institute_of_Neurological_Disorders_and Stroke. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Panagiotis Mastorakos, Matthew V. Russo, Tianzan Zhou, Kory Johnson,
Dorian B. McGavern. Antimicrobial immunity impedes CNS vascular
repair following brain injury. Nature Immunology, 2021; DOI:
10.1038/s41590-021- 01012-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210923115556.htm

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