Understanding how different brain cells respond to Stroke

A stroke occurs when blood flow to the brain is suddenly disrupted, preventing brain cells from getting the oxygen and nutrients they need. There are two main types of strokes: ischemic stroke, which accounts for about 87% of all strokes and occurs when a blood vessel supplying blood to the brain is obstructed, and haemorrhagic stroke, which happens when a blood vessel in the brain bursts. Strokes can lead to significant disabilities and are a major cause of death worldwide.

Stroke is a pressing global health issue. According to recent statistics, every 40 seconds, someone experiences a stroke, and every 3 minutes and 11 seconds, someone dies from one​. In the UK, 100,000 people have strokes each year, and there are around 1.3 million stroke survivors. Moreover, the risk of stroke is particularly high among certain populations, with non-Hispanic Black adults being nearly twice as likely to suffer a stroke compared to their White counterparts​.

The role of brain cells, including astrocytes (star-shaped brain cells that support and nourish neurons, maintaining the blood-brain barriers integrity and function, and assist in healing after injury) and oligodendrocyte precursor cells (OPCs) (responsible for creating myelin, which insulates nerve fibres and enhances signal transmission), in the brain’s response to stroke has become an important area of study. These cells are essential for maintaining brain health, managing inflammation, and facilitating repair after injury. However, our understanding of how different types of these supportive cells respond during the acute phase (the initial period after a stroke occurs, usually lasting a few hours or days) of a stroke remains limited​.

This study utilises advanced techniques to closely examine how glial cells behave immediately following a stroke. By looking at the individual responses of astrocytes and OPCs, we aim to identify the unique and shared ways these cells react to injury. Our findings could deepen our understanding of the inflammatory processes following a stroke and may lead to new treatment strategies to promote recovery and repair in the brain.

Why is the study important?

This study is important because it helps us understand how different brain cells react after an ischemic stroke. By examining the interactions between supportive cells in the brain, researchers aim to find better treatments that not only restore blood flow but also promote healing. They used advanced techniques to closely analyse individual brain cells, revealing how they communicate and respond to injury. The insights gained from this research could also help in understanding other brain conditions, potentially leading to new therapies for various neurological problems.

What did the authors do and how did they do it?

The researchers induced ischaemic stroke in male rats and mice to explore how the brain reacts to this type of injury, which happens when blood flow to a part of the brain is blocked, causing cell damage. They used a method called single-nucleus RNA sequencing (snRNA-seq) to look at the different types of brain cells and how their gene activity changed after the stroke. This technique lets scientists examine gene expression (the process by which a gene’s information is used to create molecules that carry out specific functions in the body and contribute to visible traits or characteristics) at the level of individual cells.

The study focused on significant changes in the gene activity of the supportive cells after the stroke. Using magnetic resonance imaging (MRI) (a non-invasive imaging technology that produces three dimensional detailed images of tissues), they confirmed the presence of lesions in the brain 48 hours after the stroke was induced. The researchers isolated the nuclei (the central and most important part of a cell, forming the basis for its activity and growth) from individual brain cells to analyse gene expression and used statistical software to identify genes that were either turned on or off in response to the stroke. They also stained the brain tissue to visualise the location of the affected cells.

Finally, the researchers examined which biological functions were connected to the genes with changed activity, offering important insights into how the brain reacts to injury.

Researchers found that following a stroke, there are significant changes in the types and activities of brain cells, particularly cells like oligodendrocytes and astrocytes.

These cells showed distinct responses depending on the severity of the stroke, with certain OPCs and astrocytes growing rapidly in areas affected by the stroke. The study also highlighted important interactions between these cells and immune cells, specifically myeloid cells, which play a role in the brain’s response to injury.

Notably, a protein called osteopontin was found to enhance the movement of OPCs, suggesting it might be crucial for recovery processes after a stroke.

What do the findings mean going forward for people with the disease?

Overall, the findings provide valuable insights into the cellular activity following stroke and highlight the importance of cell communication, which could inform future therapeutic strategies aimed at promoting brain recovery.

The study’s findings have significant implications for future stroke research and treatment. By providing detailed insights into how different brain cell types respond in the acute phase after a stroke, this research opens doors to more targeted therapeutic approaches. The identification of specific cell types and molecular interactions involved in the brain’s response to stroke damage offers potential new targets for therapies aimed at promoting recovery. Notably, the study highlights the crucial role of cells, such as oligodendrocytes and astrocytes, in responding to stroke, suggesting that future treatments may focus more on supporting or modulating these cells’ activities.

The revealed interactions between immune cells and certain brain cells in stroke-affected areas indicate that managing the immune response could be key in stroke recovery. The discovery of proliferating oligodendrocyte precursor cells (OPCs) and their interactions hints at the brain’s natural repair mechanisms, which future therapies might aim to enhance. Additionally, the study’s finding that osteopontin, a protein produced by immune cells, may influence OPC movement could lead to new approaches in promoting brain repair.

Importantly, the research focused on the brain’s response 48 hours after stroke, emphasising the critical nature of early intervention and the potential for time-sensitive treatments in the acute phase of stroke recovery.

This study can be found at
https://doi.org/10.1038/s41467-024-50465-z 

Paper title
Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents

Lead author
Daniel Bormann & Michael Mildner

Publication details including date of publication
Nature Communications, 24 July 2024