Research has attributed tissue damage post-traumatic brain injury (TBI) to two-pronged effects, increased reactive oxygen species (ROS) and impairment of endogenous antioxidant defence systems, underpinned by manganese superoxide dismutase (MnSOD). Novel antioxidant nitroxides have been shown to mimic MnSOD to ameliorate oxidative stress related disorders. This study aimed to investigate the effects of two nitroxides, CTMIO and DCTEIO, on the neurological outcomes following moderate TBI in rats induced by a weight drop device. The rats were immediately treated with CTMIO and DCTEIO (40 mM in drinking water) post-injury for up to 2 weeks. The brains were histologically examined at 24 h and 6 weeks post injury. DCTEIO reduced the lesion size at both 24h and 6 weeks, with normalised performance in sensory, motor and cognitive tests at 24h post-injury. Astrogliosis was heightened by DCTEIO at 24h and still elevated at 6 weeks in this group. In TBI brains, cellular damage was evident as reflected by changes in markers of mitophagy and autophagy (increased fission marker dynamin-related protein (Drp)-1, and autophagy marker light chain 3 (LC3)A/B and reduced fusion marker optic atrophy (Opa)-1). These were normalised by DCTEIO treatment. CTMIO, on the other hand, seems to be toxic to the injured brains, by increasing injury size at 6 weeks. In conclusion, DCTEIO significantly improved tissue repair and preserved neurological function in rats with TBI possibly via a mitophagy mechanism. This study provides evidence for DCTEIO as a promising new option to alleviate lesion severity after moderate TBI, which is not actively treated.

中文翻译：

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一氧化氮会影响大鼠脑外伤模型引起的神经功能缺损和病变大小。

研究已将组织损伤在颅脑外伤后（TBI）归因于两管齐下的作用，增加的活性氧（ROS）和以锰超氧化物歧化酶（MnSOD）为基础的内源性抗氧化防御系统的损伤。新型抗氧化剂氮氧化物已被证明可模仿MnSOD来缓解与氧化应激相关的疾病。这项研究的目的是研究由减肥设备诱发的大鼠中度TBI后两种神经氧化物CTMIO和DCTEIO对神经系统预后的影响。损伤后立即用CTMIO和DCTEIO（饮用水中40 mM）治疗大鼠长达2周。在受伤后24小时和6周对脑进行组织学检查。DCTEIO在损伤后24h和6周都缩小了病变的大小，并且在损伤后24h的感觉，运动和认知测试中表现正常。该组24小时DCTEIO加剧了星形胶质沉着症，并在6周时仍升高。在TBI大脑中，明显的细胞损伤表现为线粒体和自噬标记物的变化（裂变标记物动力蛋白相关蛋白（Drp）-1和自噬标记物轻链3（LC3）A / B的增加和融合标记物视神经萎缩的减少） （Opa）-1）。通过DCTEIO处理将其标准化。另一方面，CTMIO通过增加6周时的损伤大小，似乎对受伤的大脑有毒。总之，DCTEIO可能通过线粒体吞噬机制显着改善了TBI大鼠的组织修复和神经功能。这项研究为DCTEIO作为减轻中度TBI（未积极治疗）后病变严重程度的有希望的新选择提供了证据。