Abstract：
To date, no therapy has been proven to be efficacious in fully restoring neurological functions after spinal cord injury (SCI). Systemic high-dose methylprednisolone (MP) improves neurological recovery after acute SCI in both animal and human. MP therapy remains controversial due to its modest effect on functional recovery and significant adverse effects. To overcome the limitation of MP therapy, we have developed a N-(2-hydroxypropyl) methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP) that can selectively deliver MP to the SCI lesion when administered systemically in a rat model of acute SCI. Our in vivo data reveal that Nano-MP is significantly more effective than free MP in attenuating secondary injuries and neuronal apoptosis. Nano-MP is superior to free MP in improving functional recovery after acute SCI in rats. These data support Nano-MP as a promising neurotherapeutic candidate, which may provide potent neuroprotection and accelerate functional recovery with improved safety for patients with acute SCI.
摘要：
迄今为止,在脊髓损伤（SCI）后，没有任何治疗方法可有效恢复神经功能。全身高剂量甲基强的松龙（MP）可改善动物和人类急性SCI后的神经系统恢复。MP治疗由于其对功能恢复的适度影响和显著的不良反应而仍存在争议。为了克服MP治疗的局限性，我们已经开发了一种基于N-(2-羟丙基)甲基丙烯酰胺共聚物的MP前药纳米药物(Nano-MP),当在急性SCI大鼠模型中全身给药时,它可以选择性地将MP递送至SCI病变。我们的体内数据表明，Nano-MP在减轻继发性损伤和神经元凋亡方面比游离MP有效得多。Nano-MP在改善大鼠急性SCI后功能恢复方面优于游离MP。这些数据支持Nano-MP作为一种有前途的神经治疗候选药物，这可能为急性SCI患者提供有效的神经保护并加速功能恢复，并提高安全性。
