Researchers from the National Institutes of Health have discovered Jekyll and Hyde immune cells in the brain that eventually help with brain repair but soon after an injury can cause fatal inflammation, suggesting that the time to be necessary when administering treatment. These dual-purpose cells, called myelomonocytic cells and transported to the brain by the blood, are just one type of brain immune cell discovered by NIH researchers, looking in real time while the brain was repairing itself after an injury. The study, published in Ignorance of nature, supported by the NIH National Institute of Neurological Disorders and Stroke Disorders (NINDS) Intramural Research Program.
Repairing the brain after an injury is a well-coordinated process, and giving the right treatment at the right time can do more harm than good. “
Dorian McGavern, Ph.D., NINDS Scientist and Lead Author of the Study
Cerebrovascular injuries, or damage to brain blood vessels, can occur after a number of conditions including traumatic brain injury or stroke. Dr. McGavern, along with Larry Latour, MD, a NINDS scientist, and their colleagues, claimed that a subset of stroke patients developed inflammation and inflammation in the brain after clot surgery. blood vessel responsible for the stroke. Inflammation, also known as edema, can lead to serious consequences and can be fatal as it strains brain structures and causes further damage.
To understand how vascular injury can lead to inflammation and to identify possible treatment strategies, Dr. McGavern and his team developed an animal model of cerebrovascular injury and used new microscopic imaging. modern to see how the brain dealt with the damage in real time.
Immediately after an injury, brain immune cells called microglia move rapidly to stop blood vessels from leaking. These “first responders” of the immune system expand and wrap their arms around broken blood vessels. Dr. McGavern’s group found that microglia removal causes bleeding and unstable brain damage.
A few hours later, the damaged brain is attacked by circulating peripheral monocytes and neutrophils (or, myelomonocytic cells). As myelomonocytic cells move from the blood into the brain, they all open a small hole in the vasculature, causing a mist of fluid to enter the brain. When thousands of these cells rupture into the brain at once, a lot of fluid enters at once and leads to inflammation.
“The myelomonocytic cells at this stage of repair are well-intentioned, and want to help, but they enter the brain with too much energy. This can lead to terrible damage and muscle tension, especially if it occurs around the brain ‘s gas, which controls vital functions, such as breathing, “said Dr McGavern.
After this initial increase, a monocytic subset of immune cells enters the brain at a slower, less destructive rate and gets to work repairing the vessels. Monocytes work in repair-related microglia to rebuild the damaged vascular network, which is reconnected within 10 days of injury. The monocytes are needed for this important repair process.
In the next set of experiments, Dr. McGavern and his colleagues attempted to reduce secondary and thin tissue damage by using a combination of therapeutic antibodies that stop myelomonocytic cells from invading. to the brain. The antibodies inhibited two different adhesion molecules that myelomonocytic cells use to bind to inflamed blood vessels. These were effective in reducing brain inflammation and improving outcomes when administered within six hours of injury.
Interestingly, the therapeutic antibodies did not work if given after six hours or if given too long. In fact, treating mice over a series of days with these antibodies prevented the proper repair of damaged blood vessels, leading to neuronal death and brain scarring.
“The time is crucial when you are trying to prevent fatal edema. You want to prevent inflammation and severe brain damage, but you do not want to prevent the monocytes from the beneficial repair work them, “Dr McGavern said.
Plans are currently underway for clinical trials to see if administering medications at specific times will reduce edema and brain damage in a subset of patients with stroke. Future research studies will examine additional aspects of the cerebrovascular repair process, with the hope that other therapeutic interventions will be identified to promote regenerative immune functions.
This study was supported by the NINDS Intramural Research Program.
Source:
NIH / National Institute of Neurological Disorders and Stroke