Researchers conducted a study to investigate the immediate aftermath of a stroke within the stem cell niche, specifically the subventricular zone, using a mouse model. Their findings uncovered a mechanism that leads to a decrease in the survival of newly formed neurons from this stem cell niche following a stroke, which in turn hampers the subventricular zone’s ability to regenerate the brain. Gaining insight into these cellular processes in the brain could pave the way for future strategies to enhance the body’s natural repair mechanisms, helping to replace lost neurons and mitigate the effects of a stroke.
A team from the University of Freiburg explored the events that unfold right after a stroke in the subventricular zone—known as a stem cell niche—using a mouse model. Their research uncovered a mechanism that results in a reduced number of surviving new neurons from the stem cell niche after a stroke, significantly limiting the neurogenic response in the subventricular zone that is crucial for brain repair. This basic understanding of brain cellular processes could potentially support future efforts to enhance the body’s natural repair systems to replace lost neurons and reduce stroke impact.
In healthy brains of rodents, new neurons are continuously formed in the subventricular zone (SVZ), a designated stem cell niche. These neurons potentially aid in repairing damage caused by central nervous system disorders. In response to brain injury, the SVZ generates new neurons that migrate to the damaged area, providing cellular support. However, after a stroke, the body’s repair system—specifically the neurogenic response of the SVZ—is notably impaired. Researchers, led by Prof. Dr. Christian Schachtrup from the Institute of Anatomy and Cell Biology at the University of Freiburg, along with his former doctoral student Dr. Suvra Nath, have investigated the underlying mechanisms responsible for this limited repair response.
Stroke adversely affects microglia and neuron interactions
Following a stroke, the blood vessel system within the SVZ becomes more permeable. This change allows proteins such as fibrinogen to enter the stem cell niche, which in turn alters the activity of local microglia cells. These immune cells in the central nervous system are rapidly activated due to changes in the stem cell environment, impacting the cell cycle of the neural stem cells and leading to the death of new neurons. “The SVZ stem cell niche is inherently delicate. Microglia, acting as the brain’s defense cells, are essential for maintaining the specific microenvironment of the SVZ and regulate the actions of neural stem cells. However, these interactions are disrupted following a stroke,” Schachtrup explains.
A testing approach indicated that the interaction between activated microglia and neural stem cells negatively affects the brain’s ability to repair itself: when the original microenvironment of the SVZ is reinstated, neurogenic repair increases—even after a stroke. Moreover, reducing the number of activated microglia leads to a higher survival rate of new neurons within the SVZ.
Reducing stroke impact
The processes identified by the researchers begin almost immediately after the stroke occurs. To unveil these mechanisms, they relied on mouse models since, unlike rodents, the human brain only produces new neurons during the first year of life, with this production ceasing afterwards. The researchers speculate that it may be feasible to reactivate this production through medical interventions. “By understanding how neural stem cells differentiate and how external factors influence the formation of new neurons, we can advance our efforts to promote the brain’s inherent repair mechanisms in central nervous system disorders,” states Schachtrup. Future research will involve exploring the interactions between microglia and neural stem cells in human organoids, bringing them closer to elucidating similar processes in the human brain.
