Scientists from the University of Freiburg used a mouse model to analyze what happens immediately after a stroke in a stem cell area of interest called the subventricular zone. This revealed a mechanism that causes fewer newborn neurons from the stem cell area of interest to survive after stroke, significantly reducing the neurogenic response of the subventricular zone to repair the brain. This fundamental understanding of cellular processes within the brain may in the longer term help speed up the body’s repair processes to exchange lost neurons and alleviate the consequences of stroke.

Within the brains of healthy rodents, newborn neurons are generated constantly in a stem cell area of interest called the subventricular zone (SVZ). These cells may help repair the brain damaged by central nervous system disorders. After brain damage, the SVZ responds by generating newborn neurons that migrate toward the lesion area and may provide cell alternative there. Nevertheless, after a stroke, the functioning of the body’s own repair system, the SVZ neurogenic response, may be very limited. Scientists led by prof. Dr. Christian Schachtrup, professor on the Institute of Anatomy and Cell Biology on the University of Freiburg, and his former PhD student, Dr. Suvra Nath, investigated the mechanisms underlying this limited brain repair response.

Stroke negatively affects the interaction of microglia and neurons

The vascular system, or SVZ, becomes more permeable after a stroke. Consequently, fibrinogen and other proteins reach the stem cell area of interest, which in turn affects local microglial cells. These central nervous system immune cells are immediately activated by changes within the stem cell area of interest, affecting neural stem cell cell cycle progression, resulting in cell death of newborn neurons. “The SVZ stem cell area of interest is a fragile system. Microglia, the defense cells of the brain, are an integral a part of the characteristic microenvironment of the SVZ and regulate the behavior of neural stem cells. These interactions within the stem cell area of interest are disrupted after a stroke,” explains Schachtrup.

A follow-up assay also suggests that interactions between activated microglia and neural stem cells within the SVZ negatively impact neurogenic repair: restoring the unique SVZ microenvironment increases neurogenic repair – even after stroke. At the identical time, more newborn neurons survive within the SVZ if the variety of activated microglial cells is reduced.

Mitigating the consequences of a stroke

The processes described by the researchers begin shortly after a stroke. To grasp them, that they had to depend on mouse models. Although the human brain also has an SVZ, recent neurons are usually not formed until the primary 12 months of life and cell production then becomes dormant. Scientists imagine it is feasible to boost this production through medical intervention.

Once we understand the mechanisms of neural stem cell differentiation and the influence of extracellular aspects on the event of newborn neurons, it’ll bring us closer to promoting endogenous brain repair in central nervous system disorders.”

Dr. Christian Schachtrup, professor on the Institute of Anatomy and Cell Biology of the University of Freiburg

Next, the researchers want to analyze the interactions between microglia cells and neural stem cells in human organoids. This method brings them closer to their goal of understanding similar processes occurring within the human brain.