Kim Jong-Wan, Mahapatra Chinmaya, Hong Jin-Young, Kim Min Soo, Leong Kam W, Kim Hae-Won, Hyun Jung Keun
Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine Dankook University Cheonan 330-714 Republic of Korea.
Institute of Tissue Regeneration Engineering (ITREN) Dankook University Cheonan 330-714 Republic of Korea.
Adv Sci (Weinh). 2017 Jul 8;4(10):1700034. doi: 10.1002/advs.201700034. eCollection 2017 Oct.
Spinal cord injury (SCI) produces excess reactive oxygen species (ROS) that can exacerbate secondary injury and lead to permanent functional impairment. Hypothesizing that cerium oxide nanoparticles (CONPs) as an effective ROS scavenger may offset this damaging effect, it is first demonstrated in vitro that CONPs suppressed inducible nitric oxide synthase (iNOS) generation and enhanced cell viability of hydrogen peroxide (HO)-insulted cortical neurons. Next, CONPs are administered at various does (50-4000 µg mL) to a contused spinal cord rat model and monitored the disease progression for up to eight weeks. At one day postinjury, the number of iNOS+ cells decreases in the treated groups compared with the control. At one week, the cavity size and inflammatory cells are substantially reduced, and the expression of proinflammatory and apoptotic molecules is downregulated with a concurrent upregulation of anti-inflammatory cytokine. By eight weeks, the treated groups show significantly improved locomotor functions compared with the control. This study shows for the first time that injection of optimal-dosed CONPs alone into contusion-injured spinal cord of rats can reduce ROS level, attenuate inflammation and apoptosis, and consequently help locomotor functional recovery, adding a promising and complementary strategy to the other treatments of acute SCI.
脊髓损伤（SCI）会产生过量的活性氧（ROS），这会加剧继发性损伤并导致永久性功能障碍。假设氧化铈纳米颗粒（CONPs）作为一种有效的ROS清除剂可能抵消这种损伤作用，首先在体外证明CONPs可抑制诱导型一氧化氮合酶（iNOS）的产生，并提高过氧化氢（HO）损伤的皮质神经元的细胞活力。接下来，将不同剂量（50 - 4000 µg/mL）的CONPs施用于脊髓挫伤大鼠模型，并监测疾病进展长达八周。在损伤后一天，与对照组相比，治疗组中iNOS+细胞的数量减少。在一周时，空洞大小和炎性细胞显著减少，促炎和凋亡分子的表达下调，同时抗炎细胞因子上调。到八周时，与对照组相比，治疗组的运动功能有显著改善。这项研究首次表明，单独向大鼠挫伤性脊髓损伤部位注射最佳剂量的CONPs可降低ROS水平，减轻炎症和凋亡，从而有助于运动功能恢复，为急性SCI的其他治疗增添了一种有前景的补充策略。
