A facilitatory role of astrocytes in axonal regeneration after acute and chronic spinal cord injury

IF 4.6 2区 医学 Q1 NEUROSCIENCES Experimental Neurology Pub Date : 2024-07-15 DOI:10.1016/j.expneurol.2024.114889
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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 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.

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星形胶质细胞在急性和慢性脊髓损伤后轴突再生中的促进作用
神经科学教条认为,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,最近的一份报告指出,星形胶质细胞在病变周围形成的 "边界 "对轴突生长是允许性的,而不是抑制性的。现在,我们提供了进一步的证据,支持星形胶质细胞在脊髓损伤后的轴突再生中发挥促进作用。首先,即使在 SCI 6 个月后,受伤的轴突仍能保留在密集反应的星形胶质细胞区域内,与星形胶质细胞过程直接接触而不被排斥。其次,延迟6个月植入的神经干细胞可将轴突延伸至病变周围的反应性星形胶质细胞边界,密集接触星形胶质细胞表面。第三,将生物工程水凝胶植入脊髓损伤部位,可重新定向反应性星形胶质细胞过程,使其沿着脊髓喙向尾轴线排列,从而成功再生到与星形胶质细胞过程密切相关的病变/支架部位。第四,皮质脊髓轴突再生到损伤后六个月植入的神经祖细胞中,与宿主星形胶质细胞过程紧密结合。因此,星形胶质细胞似乎并不抑制轴突再生,而新生长的轴突与星形胶质细胞过程的密切联系表明,星形胶质细胞在轴突再生中起着促进作用。
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来源期刊
Experimental Neurology
Experimental Neurology 医学-神经科学
CiteScore
10.10
自引率
3.80%
发文量
258
审稿时长
42 days
期刊介绍: Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.
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