VA San Diego Healthcare System, San Diego, CA, USA; Dept. of Neurosciences, University of California - San Diego, La Jolla, CA, USA.
Dept. of Neurosciences, University of California - San Diego, La Jolla, CA, USA.
Exp Neurol. 2024 Sep;379:114889. doi: 10.1016/j.expneurol.2024.114889. Epub 2024 Jul 15.
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 permissive rather than inhibitory to axonal growth. We now provide further evidence supporting a facilitatory role of astrocytes in axonal regeneration after SCI. First, even 6months 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 into the lesion/scaffold in close association with astrocytic processes. Fourth, corticospinal axons regenerate into neural progenitor cells implanted six months after injury in close association with host astrocytic processes. Thus, astrocytes do not appear to inhibit axonal regeneration, and the close association of newly growing axons with astrocytic processes suggests a facilitatory role in axonal regeneration.
神经科学的教条认为，星形胶质细胞的“疤痕”会抑制脊髓损伤（SCI）后的轴突再生。然而，最近的一份报告表明，星形胶质细胞在损伤周围形成“边界”，这些边界对轴突生长是允许的，而不是抑制的。我们现在提供了更多支持星形胶质细胞在 SCI 后轴突再生中具有促进作用的证据。首先，即使在 SCI 后 6 个月，受损的轴突仍保留在密集反应性星形胶质细胞区域内，与星形胶质细胞突起直接接触而不被排斥。其次，神经干细胞的 6 个月延迟植入可将轴突延伸到损伤周围的反应性星形胶质细胞边界，与星形胶质细胞表面紧密接触。第三，植入 SCI 部位的生物工程水凝胶使反应性星形胶质细胞突起重新定向，沿着脊髓的头侧到尾侧轴排列，导致成功地再生到损伤/支架中，与星形胶质细胞突起密切相关。第四，皮质脊髓轴突在损伤后 6 个月与宿主星形胶质细胞突起密切相关，再生到植入的神经祖细胞中。因此，星形胶质细胞似乎不会抑制轴突再生，并且新生长的轴突与星形胶质细胞突起的密切关联表明它们在轴突再生中具有促进作用。
