The Chronic Glial Border Does Not Inhibit Axonal Regeneration After Spinal Cord Injury

Abstract Neuroscience dogma avers that astrocytic “scars” inhibit axonal regeneration after spinal cord injury (SCI). A recent report suggested however that astrocytes form “borders” around lesions that are not inhibitory and may be permissive to axonal growth, although direct evidence is lacking. We now provide direct evidence that astrocytes support axonal growth after SCI. First, even 6 months after SCI, injured axons are retained within regions of densely reactive astrocytes, in direct contact with astrocyte processes without being repelled. Second, 6 month-delayed implants of neural stem cells extend axons into reactive astrocyte borders surrounding lesions, densely contacting astrocyte surfaces. Third, bioengineered hydrogels implanted into sites of SCI re-orient reactive astrocytic processes to align along the rostral-to-caudal spinal cord axis resulting in successful regeneration along astrocytic processes. Fourth, corticospinal axons regenerate into neural stem cells implanted six months after injury in close association with host astrocytic processes. Thus, astrocytes support axonal regeneration.