Rationale: Autophagy in Schwann cells (SCs) is crucial for myelin debris degradation and clearance following peripheral nerve injury (PNI). Nerve growth factor (NGF) plays an important role in reconstructing peripheral nerve fibers and promoting axonal regeneration. However, it remains unclear if NGF effect in enhancing nerve regeneration is mediated through autophagic clearance of myelin debris in SCs.

Methods: In vivo, free NGF solution plus with/without pharmacological inhibitors were administered to a rat sciatic nerve crush injury model. In vitro, the primary Schwann cells (SCs) and its cell line were cultured in normal medium containing NGF, their capable of swallowing or clearing degenerated myelin was evaluated through supplement of homogenized myelin fractions.

Results: Administration of exogenous NGF could activate autophagy in dedifferentiated SCs, accelerate myelin debris clearance and phagocytosis, as well as promote axon and myelin regeneration at early stage of PNI. These NGF effects were effectively blocked by autophagy inhibitors. In addition, inhibition of the p75 kD neurotrophin receptor (p75^NTR) signal or inactivation of the AMP-activated protein kinase (AMPK) also inhibited the NGF effect as well.

Conclusions: NGF effect on promoting early nerve regeneration is closely associated with its accelerating autophagic clearance of myelin debris in SCs, which probably regulated by the p75^NTR/AMPK/mTOR axis. Our studies thus provide strong support that NGF may serve as a powerful pharmacological therapy for peripheral nerve injuries.

原理：雪旺细胞（SCs）中的自噬对于髓鞘碎片的降解和周围神经损伤（PNI）后的清除至关重要。神经生长因子（NGF）在重建周围神经纤维和促进轴突再生中起重要作用。但是，尚不清楚NGF促进神经再生的作用是否通过自噬清除SC中的髓磷脂碎片来介导。

方法：在体内，将游离NGF溶液加或不加药理抑制剂用于大鼠坐骨神经挤压伤模型。在体外，将原代雪旺氏细胞（SCs）及其细胞系在含有NGF的正常培养基中培养，通过补充均质的髓磷脂级分来评估其吞咽或清除变性髓鞘的能力。

结果：外源性NGF的给药可以激活去分化SC中的自噬，加速髓鞘碎片的清除和吞噬作用，并促进PNI早期的轴突和髓鞘再生。这些NGF的作用被自噬抑制剂有效地阻止了。此外，抑制p75 kD神经营养蛋白受体（p75 ^NTR）信号或AMP激活的蛋白激酶（AMPK）失活也同样抑制了NGF的作用。

结论：NGF促进早期神经再生的作用与其促进SCs中髓鞘碎片的自噬清除有关，这可能受p75 ^NTR / AMPK / mTOR轴调控。因此，我们的研究提供了有力的支持，认为NGF可以作为治疗周围神经损伤的有力药物。