School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China; Brain Research Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China.
Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China.
Free Radic Biol Med. 2019 Nov 1;143:454-470. doi: 10.1016/j.freeradbiomed.2019.08.029. Epub 2019 Aug 28.
Brachial plexus avulsion (BPA) occurs when the spinal nerve roots are pulled away from the surface of the spinal cord and disconnects neuronal cell body from its distal downstream axon, which induces massive motoneuron death, motor axon degeneration and de-innervation of targeted muscles, thereby resulting in permanent paralysis of motor functions in the upper limb. Avulsion injury triggers oxidative stress and intense local neuroinflammation at the lesioned site, leading to the death of most motoneurons. Berberine (BBR), a natural isoquinoline alkaloid derived from medicinal herbs of Berberis and Coptis species, has been reported to possess neuro-protective, anti-inflammatory and anti-oxidative effects in various animal models of central nervous system (CNS)-related disorders. In this study, we aimed to investigate the effect of BBR on motoneuron survival and axonal regeneration following spinal root avulsion plus re-implantation in rats. Our results indicated BBR significantly accelerated motor function recovery in the forelimb as revealed by the increased Terzis grooming test score, facilitated motor axon regeneration as evidenced by the elevated number of Fluoro-Gold-labeled and P75-positive regenerative motoneurons. The survival of motoneurons was notably promoted by BBR administration presented with boosted ChAT-immunopositive and neutral red-stained neurons. BBR treatment efficiently alleviated muscle atrophy, attenuated functional motor endplates loss in biceps and prevented the reduction of motor axons in the musculocutaneous nerve. Additionally, BBR treatment markedly mitigated the avulsion-induced neuroinflammation via inhibiting microglial and astroglial reactivity, up-regulated the expression of antioxidative indicator Cu/Zn SOD, and down-regulated the levels of nNOS, 3-NT, lipid peroxidation and NF-κB, as well as promoted SIRT1, PI3K and Akt activation. Collectively, BBR might be a promising therapy to assist re-implantation surgery for the treatment of BPA.
臂丛神经根撕脱伤（BPA）是指脊髓神经根从脊髓表面被牵拉，导致神经元细胞体与其远端下游轴突分离，从而引起大量运动神经元死亡、运动轴突退化和靶向肌肉去神经支配，导致上肢运动功能永久瘫痪。撕脱伤会引发损伤部位的氧化应激和强烈的局部神经炎症，导致大多数运动神经元死亡。小檗碱（BBR）是一种从小檗属和黄连属植物中提取的天然异喹啉生物碱，已被报道在多种与中枢神经系统（CNS）相关疾病的动物模型中具有神经保护、抗炎和抗氧化作用。在这项研究中，我们旨在研究 BBR 对大鼠脊髓神经根撕脱再植入后运动神经元存活和轴突再生的影响。我们的结果表明，BBR 显著加速了前肢的运动功能恢复，表现在增加了特泽斯梳理试验评分，促进了运动轴突再生，表现为 Fluoro-Gold 标记和 P75 阳性再生运动神经元数量的增加。BBR 给药显著促进了运动神经元的存活，表现为 ChAT 免疫阳性和中性红染色神经元数量的增加。BBR 治疗可有效减轻肌肉萎缩，减轻二头肌功能性运动终板的丧失，并防止肌皮神经中运动轴突的减少。此外，BBR 治疗通过抑制小胶质细胞和星形胶质细胞的反应性、上调抗氧化指标 Cu/Zn SOD 的表达、下调 nNOS、3-NT、脂质过氧化和 NF-κB 的水平以及促进 SIRT1、PI3K 和 Akt 的激活，显著减轻了撕脱伤引起的神经炎症。总之，BBR 可能是一种有前途的治疗方法，可辅助再植入手术治疗 BPA。
