Spinal cord injury (SCI) is a devastating condition of the central nervous system that can lead to permanent motor and sensory deficits. Carbon monoxide-releasing molecule-2 (CORM-2) has been shown to have anti-inflammatory, anti-apoptotic, and angiogenic properties that may be useful for the treatment of SCI. However, it has a short carbon monoxide (CO) release half-life (approximately 1 min). To address this challenge, we developed a CORM-2-incorporated solid lipid nanoparticle (CORM-2-SLN) and evaluated its ameliorating effects for preventing blood-spinal cord barrier (BSCB) disruption and endothelial cell death following SCI. After a moderate compression injury of the spinal cord (compression with a 35-g impounder for 5 min), groups of rats were treated with a CORM-2-solution and CORM-2-SLNs at an equal dose of 10 mg/kg each via an intraperitoneal injection for 8 consecutive days. Behavior analysis was performed and animals were later sacrificed at different time points and evaluated for whether the CORM-2-SLNs prevented BSCB disruption and rescued endothelial cell damage following SCI. The CORM-2-SLN-treated group showed significantly diminished extravasation of Evans Blue dye with enhanced expression of tight junction proteins following SCI. Likewise, significantly diminished endothelial cell markers after SCI were optimally stabilized at 21 days. Additionally, lipopolysaccharide (LPS)-induced loss of tight junction integrity was significantly preserved after CORM-2-SLN treatment in human cerebral microvascular endothelial cell line (hCMEC/D3). Clinically, CORM-2-SLNs were associated with a significantly improved functional recovery, as compared with the CORM-2-solution. CORM-2-SLNs may help potentially to maintain BSCB integrity following SCI.

中文翻译：

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脊髓损伤后，CORM-2-固溶脂质纳米颗粒可维持血脊髓屏障的完整性。

脊髓损伤（SCI）是中枢神经系统的破坏性疾病，可能导致永久性运动和感觉缺陷。一氧化碳释放分子2（CORM-2）已被证明具有抗炎，抗凋亡和血管生成特性，可用于治疗SCI。但是，它的一氧化碳（CO）释放半衰期很短（约1分钟）。为了解决这一挑战，我们开发了一种结合CORM-2的固体脂质纳米颗粒（CORM-2-SLN），并评估了其预防SCI后防止血脊髓屏障（BSCB）破坏和内皮细胞死亡的改善作用。脊髓受到中等程度的压迫损伤后（用35 g撞击器压迫5分钟），各组大鼠通过腹膜内注射以相等的剂量分别以10mg / kg的CORM-2-溶液和CORM-2-SLNs治疗8天。进行行为分析，然后在不同的时间点处死动物，并评估CORM-2-SLN是否在SCI后预防BSCB破坏并挽救了内皮细胞损伤。CORM-2-SLN治疗组在SCI后显示出伊文思蓝染料的外渗显着减少，紧密连接蛋白表达增强。同样，SCI后的内皮细胞标记物明显减少，可在21天时达到最佳稳定状态。此外，在人脑微血管内皮细胞系（hCMEC / D3）中，CORM-2-SLN处理后，脂多糖（LPS）引起的紧密连接完整性的丧失得以显着保留。临床上 与CORM-2-solution相比，CORM-2-SLN与功能恢复显着相关。在SCI之后，CORM-2-SLN可能有助于潜在地维护BSCB完整性。