Spinal cord injury (SCI) often causes severe and permanent disabilities due to the regenerative failure of severed axons. Here we report significant locomotor recovery of both hindlimbs after a complete spinal cord crush. This is achieved by the unilateral transduction of cortical motoneurons with an AAV expressing hyper-IL-6 (hIL-6), a potent designer cytokine stimulating JAK/STAT3 signaling and axon regeneration. We find collaterals of these AAV-transduced motoneurons projecting to serotonergic neurons in both sides of the raphe nuclei. Hence, the transduction of cortical neurons facilitates the axonal transport and release of hIL-6 at innervated neurons in the brain stem. Therefore, this transneuronal delivery of hIL-6 promotes the regeneration of corticospinal and raphespinal fibers after injury, with the latter being essential for hIL-6-induced functional recovery. Thus, transneuronal delivery enables regenerative stimulation of neurons in the deep brain stem that are otherwise challenging to access, yet highly relevant for functional recovery after SCI.

脊髓损伤（SCI）通常由于严重的轴突再生失败而导致严重的永久性残疾。在这里，我们报告了脊髓完全挤压后，两个后肢的运动恢复显着。这可以通过表达AAV的hyper-IL-6（hIL-6），有效的细胞因子刺激JAK / STAT3信号转导和轴突再生的AAV单向转导运动神经元来实现。我们发现这些AAV转换的运动神经元的侧支投射到缝核两侧的血清素能神经元。因此，皮层神经元的转导促进了脑干中神经支配的神经元的轴突运输和hIL-6的释放。因此，hIL-6的这种跨神经元传递促进了损伤后皮质脊髓和后棘纤维的再生，后者对于hIL-6诱导的功能恢复至关重要。因此，跨神经传递可以使深部脑干中的神经元再生刺激，否则难以进入，但与SCI后的功能恢复高度相关。