Did you call the cleaners?

Immune cells clean the brain after a stroke

Kirill Stasevich, Science and Life (nkj.ru )

Cleaning up dead cells, fragments of membranes and other debris is done by special immune cells macrophages – they literally eat everything unnecessary, that is, they capture cellular outgrowths, immerse themselves inside and digest. (By the way, they eat not only the remains of dead cells, but also quite living bacteria, cancer cells and anything else that arouses suspicion.) Macrophages are actively moving in search of something to eat, and there is no place in our body where they would not be. They also exist in the brain, only here macrophage-type cells are called microglia, and in the brain they not only monitor cleanliness, but also edit neural circuits.

With the disease, there are more macrophages – they come to the focus of inflammation from the bone marrow. And the same thing happens in the brain: with Alzheimer's disease, with stroke, with multiple sclerosis, there are more cleaning cells in it. But, perhaps, the increase in the number of macrophages in the focus of the disease is only the result of the rearrangement of cells inside the brain? And maybe macrophages from the outside do not penetrate into the brain at all, and in any situation it tries to make do only with its own microglia? After all, many people have heard that in the blood vessels of the brain there is a so-called blood-brain barrier with very, very selective permeability, which prevents many molecules and cells floating in the blood from entering the brain.

Researchers from the University of Bonn, the University of Jena and their colleagues from other research centers in Germany and the United States have found a way to tag red bone marrow stem cells in mice that produced macrophages. The cells were supplied with a gene that encoded a fluorescent protein activated by the action of a certain substance. By including the fluorescent protein gene in one or another period of the mouse's life, it was possible to see how macrophages born in the bone marrow spread through the body.

If there were immune cells in the brain that came from outside, it could be seen by their glow. But, as stated in an article in Nature Neuroscience (Werner et al., Cxcr4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke), in normal, healthy mice, the brain did not glow – that is, it lacked the macrophages that it had. As already mentioned, such permanently living (or resident) macrophages exist in all tissues (only in the brain they are called microglia), and even earlier the same researchers were able to show that the first of these immune cells come to their territory during embryonic development and then manage on their own. Macrophages are able to divide themselves, and newer cells gradually replace the old ones, without needing reinforcement from the bone marrow – and the same thing happens in the brain as in other organs.

But in case of something extraordinary, reinforcements still appear. When the mice were given a stroke in the experiment, the diseased brain began to glow with new macrophages that came from the bone marrow. At first, they could be found in both living and dead nerve tissue, but after a few days, all the "alien" immune cells were grouped only in dead zones, where it was necessary to remove the dead nerve cells.

We also managed to show the importance of one of the genes that helps immune cells go where they need to go and clean up what they need. This is the Cxcr4 gene, which encodes one of the surface receptors. If the macrophages turned it off, then, firstly, they came to the brain less than usual after a stroke, and secondly, macrophages could not group in the right place in any way - many of them remained in healthy areas of the brain where their help was not needed. Finally, macrophages with the Cxcr4 receptor turned off had little active genes that help diseased tissue cope with damage, and at the same time they had too activated genes that stimulate inflammation – which is not very good, since inflammation hits healthy cells.

If we talk about practical conclusions, we can say that for effective recovery after a stroke, it is necessary to monitor how the immune system works: on the one hand, helper cells should appear in the brain that will remove molecular cellular debris, on the other hand, these assistants should work only where necessary, keeping the inflammatory the reaction is under control. Perhaps, with the help of some substances that allow controlling macrophages, it will be possible in the future to significantly accelerate the post-stroke recovery of the brain.

Portal "Eternal youth" http://vechnayamolodost.ru