Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, 35 Stirling Hwy, Perth, 6009, Western Australia, Australia.
Curtin Health Innovation Research Institute, Curtin University, Sarich Neuroscience Research Institute Building, 8 Verdun St, Nedlands, 6009, Western Australia, Australia.
Sci Rep. 2019 Oct 25;9(1):15297. doi: 10.1038/s41598-019-51886-3.
Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X receptors and Ca permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma.
中枢神经系统损伤会加剧继发性退化。先前的研究表明，视神经部分损伤后，联合应用口服和局部给予的离子通道抑制剂可以保护髓鞘并维持对继发性退化敏感的腹侧视神经的功能。然而，局部给药在临床上往往并不合适。本研究旨在比较洛美利嗪、亮蓝 G（BBG）和 YM872 联合离子通道抑制剂的全身和局部给药的疗效，这些抑制剂分别抑制电压门控钙通道、P2X 受体和 Ca 通透性 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体。视神经部分横断后，成年雌性 PVG 大鼠通过渗透微型泵将 BBG 和 YM872 直接递送至损伤部位，或通过腹腔注射，同时口服洛美利嗪，对其进行治疗。离子通道抑制剂联合应用的两种给药方式均可保持髓鞘结构。然而，无论是在损伤部位还是外周，治疗对炎症或少突胶质细胞的密度均无影响。综上所述，这些数据表明，即使在较低浓度下，联合治疗也可能有助于维持髓鞘结构，且全身和局部给药在改善神经创伤后的预后方面具有可比性。
