Delivery of neurotrophins to the spinal injury site via cellular transplants or viral vectors administration has been shown to promote recovery of locomotion in the absence of locomotor training in adult spinalized animals. These delivery methods involved risks of secondary injury to the cord and do not allow for precise and controlled dosing making them unsuitable for clinical applications. The present study was aimed at evaluating the locomotor recovery efficacy and safety of the neurotrophin BDNF delivered intrathecally to the lumbar locomotor centers using an implantable and programmable infusion mini-pump. Results showed that BDNF treated spinal cats recovered weight-bearing plantar stepping at all velocities tested (0.3-0.8 m/s). Spinal cats treated with saline did not recover stepping ability, especially at higher velocities, and dragged their hind paws on the treadmill. Histological evaluation showed minimal catheter associated trauma and tissue inflammation, underlining that intrathecal delivery by an implantable/programmable pump is a safe and effective method for delivery of a controlled BDNF dosage; it poses minimal risks to the cord and is clinically translational.

中文翻译：

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鞘内将 BDNF 输送至腰池可在脊髓损伤后重新启动行走能力


通过细胞移植或病毒载体给药将神经营养因子递送至脊髓损伤部位已被证明可以促进成年脊椎动物在缺乏运动训练的情况下的运动恢复。这些递送方法存在对脊髓造成二次损伤的风险，并且不允许精确和受控剂量，因此不适合临床应用。本研究旨在评估使用可植入可编程输注微型泵鞘内输送至腰椎运动中心的神经营养蛋白 BDNF 的运动恢复功效和安全性。结果表明，接受 BDNF 治疗的脊椎猫在所有测试速度（0.3-0.8 m/s）下都恢复了负重足底行走。用盐水治疗的脊柱猫没有恢复行走能力，尤其是在较高速度下，并且在跑步机上拖着后爪。组织学评估显示导管相关的创伤和组织炎症极小，这强调了通过可植入/可编程泵进行鞘内输送是控制 BDNF 剂量输送的安全有效的方法；它对脐带造成的风险最小，并且具有临床转化性。