Spinal cord injury (SCI) results in significant disruption of nerve fibers responsible for transmitting signals between the brain and body, often leading to partial or complete motor, sensory, and autonomic dysfunction below the injury site. Astrocytes are an important component in scar formation, crucial for suppression of injury propagation, effective wound healing, and the regulation of neuronal plasticity. Here, we identify the role of the actin-binding protein Drebrin (DBN) in reactive astrogliosis following SCI. SCI induces the upregulation of DBN in astrocytes, which controls immediate injury containment but also the long-term preservation of tissue integrity and healing in the spinal cord. DBN knockout results in enlarged spinal cord lesions, increased immune cell infiltration, and neurodegeneration. Mechanistically, DBN loss disrupts the polarization of scar border-forming astrocytes, leading to impaired encapsulation of the injury. In summary, DBN serves as a pivotal regulator of SCI outcome by modulating astrocytic polarity, which is essential for establishing a protective barrier confining the lesion site.

2nd Faculty of Medicine Charles University Prague Czech Republic

Charité Universitätsmedizin Berlin Charité Core Facility Experimental MRIs Berlin Germany

Charité Universitätsmedizin Berlin Institute of Molecular Biology and Biochemistry Berlin Germany

Department of Clinical Neurosciences John Van Geest Centre for Brain Repair University of Cambridge Cambridge UK

Faculty of Biological Sciences University of Leeds Leeds UK

Freie Universität Berlin Berlin Germany

German Center for Neurodegenerative Diseases Bonn Germany

Institute of Biochemistry Charité Universitätsmedizin Berlin Berlin Germany

Institute of Experimental Medicine Czech Academy of Sciences Prague Czech Republic

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