Using two-photon microscopy and longitudinal gene mapping in living mouse models, researchers identified a specialized population of “regenerative” astrocytes capable of repopulating damaged brain regions.
Specialized regenerative astrocytes remain at the lesion boundary and send newly generated cell nuclei gliding across long astrocytic extensions into the depleted injury core.
The image on the left shows a brain lesion (diameter: just under 0.5 mm).
“The findings of our study reveal a previously unknown ability of the adult brain to repair itself.
If those mechanisms can be selectively activated, that could help to more effectively repair damaged brain tissue, restore astrocyte networks and thus improve recovery after certain brain disorders.
Summary: Researchers discovered a previously unknown mechanism through which the adult mammalian brain repairs itself following focal injuries or autoimmune damage. Using two-photon microscopy and longitudinal gene mapping in living mouse models, researchers identified a specialized population of “regenerative” astrocytes capable of repopulating damaged brain regions.
Rather than relying solely on classical cell body division at the site of injury, these specialized astrocytes situated along the lesion perimeter send newly formed daughter cell nuclei gliding long distances through their star-shaped cellular extensions. These migrating cell nuclei repopulate the depleted lesion zone, re-establishing functional astrocyte networks.
This discovery overturns long-held assumptions regarding the limited regenerative capacity of adult glial networks, revealing molecular signaling pathways that could serve as therapeutic targets for traumatic brain injury and autoimmune conditions such as neuromyelitis optica spectrum disorder (NMOSD).
Key Facts
Overturning Dogma on Glial Regeneration: Demonstrates that the adult central nervous system possesses a previously unrecognized capability to replace lost astrocytes and restore damaged tissue architecture.
Demonstrates that the adult central nervous system possesses a previously unrecognized capability to replace lost astrocytes and restore damaged tissue architecture. Mechanism of Long-Distance Nuclear Migration: Specialized regenerative astrocytes remain at the lesion boundary and send newly generated cell nuclei gliding across long astrocytic extensions into the depleted injury core.
Specialized regenerative astrocytes remain at the lesion boundary and send newly generated cell nuclei gliding across long astrocytic extensions into the depleted injury core. Rebuilding Functional Glial Networks: Astrocytes perform vital homeostatic functions, including nutrient supply to neurons, blood flow regulation via end-feet, and extracellular ion balance, making their network reconstruction essential for neuronal survival.
Astrocytes perform vital homeostatic functions, including nutrient supply to neurons, blood flow regulation via end-feet, and extracellular ion balance, making their network reconstruction essential for neuronal survival. Targeted Clinical Applications: Holds therapeutic relevance for neurotraumatic brain injuries and rare autoimmune conditions like neuromyelitis optica spectrum disorder (NMOSD), where autoantibodies selectively destroy astrocytes.
Holds therapeutic relevance for neurotraumatic brain injuries and rare autoimmune conditions like neuromyelitis optica spectrum disorder (NMOSD), where autoantibodies selectively destroy astrocytes. Molecular Targets for Therapeutics: The team identified specific genes and signaling pathways temporarily activated during nuclear migration, providing potential targets for pharmacological interventions to accelerate brain repair.
Source: University of Zurich
The brain evidently can regenerate itself better than previously assumed after injuries or certain autoimmune diseases. Using a mouse model, researchers at the University of Zurich have demonstrated that special supporting and nourishing cells repopulate damaged areas of the brain by initially sending only newly formed cell nuclei there.
Glial cells are supporting and nourishing cells in the brain. Star-shaped glial cells called astrocytes are vital to the functioning of neurons. They supply the nerve cells with nutrients, help to regulate blood flow and keep brain tissue healthy.
It had long been assumed that when astrocytes are lost – as happens, for instance, in brain injuries or autoimmune diseases such as rare neuromyelitis optica spectrum disorder, in which the body’s own antibodies destroy these cells – the adult brain cannot fully replace them.
The image on the left shows a brain lesion (diameter: just under 0.5 mm). Around the perimeter of the lesion, the newly discovered “regenerative” astrocytes begin to seal the defect by forming long cellular extensions (shown in red). Newly formed cell nuclei (shown in blue) migrate along the cellular extensions toward the damaged area. Unaltered astrocytes (shown in green) surround the lesion area. The image on the right shows an enlargement of the marked area in the left image. Credit: Institute of Pharmacology and Toxicology, University of Zurich
Regenerative astrocytes repair damaged tissue
A new study by co-lead authors Marina Herwerth and Matthias Wyss from the Institute of Pharmacology and Toxicology at the University of Zurich (UZH) has now overturned that assumption: their research team headed by Bruno Weber discovered a specialized group of “regenerative” astrocytes in the brains of living mice that step in on the perimeter of the damaged area of the brain to rebuild the cells.
“The findings of our study reveal a previously unknown ability of the adult brain to repair itself. They point toward new ways of supporting recovery from ailments involving the loss of astrocytes,” Weber says.
Only cell nuclei migrate
The researchers used two-photon microscopy to observe the brains of living mice in real time over a period of several weeks and mapped which genes switch on in which areas of the brain. This way they were able to identify the special astrocytes that take care of rebuilding injured tissue. But those cells don’t just divide, they also perform a remarkable feat: “they send the newly formed nuclei of their daughter cells gliding across long distances to repopulate the damaged area of the brain and knit the astrocyte network back together,” Weber explains.
Starting points for targeted regeneration
The discovery of how adult brain cell nuclei migrate through the long star-shaped extensions of astrocytes to injured tissue expands comprehension of how the brain organizes and regenerates itself after certain injuries. If those mechanisms can be selectively activated, that could help to more effectively repair damaged brain tissue, restore astrocyte networks and thus improve recovery after certain brain disorders.
“We were able to identify numerous genes and signaling pathways that are temporarily activated during repair. They could serve as starting points in the future for influencing post-disease and -injury regeneration processes,” Weber stresses.
Key Questions Answered:
Q: How do “regenerative” astrocytes differ from standard cell division during tissue repair? A: Instead of whole cells migrating or simply dividing locally, these specialized astrocytes remain at the perimeter of the damaged area. They divide and send the newly formed nuclei of their daughter cells gliding long distances through their extended cellular processes directly into the injured zone to rebuild the network. Q: What conditions cause the loss of astrocytes in the adult brain? A: Astrocytes are lost during traumatic brain injuries, strokes, and specific neuroinflammatory or autoimmune conditions, most notably Neuromyelitis Optica Spectrum Disorder (NMOSD), where the body’s immune system produces autoantibodies that target and destroy astrocytes. Q: How was this nuclear migration observed in real time? A: Researchers at the University of Zurich used in vivo two-photon microscopy in living mouse models over several weeks. This allowed them to track living cells, observe nuclear movement through astrocytic branches, and map corresponding gene expression changes as the tissue repaired itself.
Editorial Notes:
This article was edited by a Neuroscience News editor.
Journal paper reviewed in full.
Additional context added by our staff.
About this neuroscience research news
Author: Kurt Bodenmueller
Source: University of Zurich
Contact: Kurt Bodenmueller – University of Zurich
Image: The image is credited to Institute of Pharmacology and Toxicology, University of Zurich
Original Research: Open access.
“Focal astrocyte loss reveals nuclear translocation during lesion repopulation” by Marina Herwerth, Matthias T. Wyss, Nicola B. Schmid, Anna Lasne, Jacqueline Condrau, Luca Ravotto, José María Mateos Melero, Andres Kaech, Gustav Bredell, Carolina Thomas, Rachel Kim, Petra Kukanja, Vladyslav L. Korobeynyk, Christine Stadelmann, Thomas Misgeld, Jeffrey L. Bennett, Sebastian Jessberger, Aiman S. Saab, Shane A. Liddelow & Bruno Weber. Nature Neuroscience
DOI:10.1038/s41593-026-02354-5
Abstract
Focal astrocyte loss reveals nuclear translocation during lesion repopulation
Astrocyte loss occurs in various neurological conditions and can disrupt local tissue homeostasis. While astrocytes surrounding border-forming lesions adopt reactive states without restoring astrocyte networks, how astrocytes respond to spatially confined astrocyte loss remains poorly understood.
Here we used longitudinal in vivo two-photon microscopy, combined with spatiotemporal transcriptional profiling, to examine astrocyte responses following focal aquaporin-4 antibody-mediated ablation in the somatosensory cortex of adult mouse brain, a model of astrocytopathy relevant to neuromyelitis optica spectrum disorder.
Here we show that perilesional astrocytes undergo pronounced structural remodeling during lesion repopulation, characterized by cell proliferation, prolonged multinucleated astrocyte states, polarized process extension into the depleted area and gradual displacement of nuclei into previously unoccupied astrocyte territories.
Spatial transcriptomics reveal an injury-associated molecular response that resolves as the astrocyte network is restored. Together, our findings delineate the spatiotemporal dynamics of astrocyte regeneration after astrocyte loss, extending current understanding of astroglial plasticity in the adult brain.
