Center for Paralysis Research, Department of Basic Medical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
J Biol Eng. 2012 Sep 14;6(1):18. doi: 10.1186/1754-1611-6-18.
Traumatic spinal cord injury (SCI) leads to serious neurological and functional deficits through a chain of pathophysiological events. At the molecular level, progressive damage is initially revealed by collapse of plasma membrane organization and integrity produced by breaches. Consequently, the loss of its role as a semi-permeable barrier that generally mediates the regulation and transport of ions and molecules eventually results in cell death. In previous studies, we have demonstrated the functional recovery of compromised plasma membranes can be induced by the application of the hydrophilic polymer polyethylene glycol (PEG) after both spinal and brain trauma in adult rats and guinea pigs. Additionally, efforts have been directed towards a nanoparticle-based PEG application.The in vivo and ex vivo applications of PEG-decorated silica nanoparticles following CNS injury were able to effectively and efficiently enhance resealing of damaged cell membranes.
The possibility for selectivity of tetramethyl rhodamine-dextran (TMR) dye-doped, PEG-functionalized silica nanoparticles (TMR-PSiNPs) to damaged spinal cord was evaluated using an ex vivo model of guinea pig SCI. Crushed and nearby undamaged spinal cord tissues exhibited an obvious difference in both the imbibement and accumulation of the TMR-PSiNPs, revealing selective labeling of compression-injured tissues.
These data show that appropriately functionalized nanoparticles can be an efficient means to both 1.) carry drugs, and 2.) apply membrane repair agents where they are needed in focally damaged nervous tissue.
外伤性脊髓损伤 (SCI) 通过一系列病理生理事件导致严重的神经和功能缺陷。在分子水平上,最初通过破裂导致的质膜组织和完整性崩溃来揭示渐进性损伤。因此,作为普遍调节和运输离子和分子的半透性屏障的作用丧失,最终导致细胞死亡。在以前的研究中,我们已经证明,在成年大鼠和豚鼠的脊髓和脑创伤后,应用亲水性聚合物聚乙二醇 (PEG) 可以诱导受损质膜的功能恢复。此外,还努力将 PEG 应用于纳米颗粒。PEG 修饰的硅纳米颗粒在 CNS 损伤后的体内和体外应用能够有效地增强受损细胞膜的再封闭。
使用豚鼠 SCI 的离体模型评估了四甲基罗丹明-葡聚糖 (TMR) 染料掺杂、PEG 功能化硅纳米颗粒 (TMR-PSiNPs) 对损伤脊髓的选择性的可能性。粉碎和附近未损伤的脊髓组织在 TMR-PSiNPs 的吸收和积累方面表现出明显的差异,表明对压缩损伤组织的选择性标记。
这些数据表明,适当功能化的纳米颗粒可以成为一种有效的手段,既能携带药物,又能在局灶性损伤的神经组织中应用膜修复剂。