Spinal cord injury (SCI)-initiated inflammation was treated with anti-inflammatory reagents. We compared local spinal cord or intraperitoneal infusion of two Myxoma virus derived immune modulating proteins, Serp-1 and M-T7, with dexamethasone (DEX). Hemorrhage and necrosis after SCI initiate a complex pathogenesis dominated by early, severe and highly destructive inflammatory macrophage infiltration. We examined sustained, 7-day, subdural infusion of either M-T7, a chemokine modulator or Serp-1, a plasminogen activator and factor inhibitor. Mature male rats had epidural balloon crush SCI and sustained subdural infusion of Serp-1, M-T7, DEX or saline for 7 days via the osmotic pump. A separate group of rats with SCI had intra-peritoneal infusion. Clinical evaluation included endpoint monitoring with body weight, hemorrhagic cystitis and bilateral toe pinch response. Sections of the spinal cord were analyzed histologically and macrophage numbers counted by standardized protocol in the cavity of injury (COI). While the rats administered DEX demonstrated substantial body weight loss, dehydration and dermal atrophy consistent with steroid toxicity, rats infused with Serp-1 and M-T7 had no toxicity. Serp-1 improved withdrawal responses. Subdural infusion of Serp-1, M-T7 and DEX significantly reduced numbers of phagocytic, CD68-positive macrophages. With intraperitoneal infusion only M-T7 reduced macrophage counts, Serp-1 showed only a trend. Local infusion of highly active immune modulating proteins; Serp-1 and M-T7, targeting serine protease and chemokine pathways demonstrated excellent potential for neuroprotection after severe SCI in a rat model, without adverse side effects. Sustained subdural infusion offers an alternative route of administration for treatment of SCI.

中文翻译：

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粘液瘤病毒衍生的免疫调节蛋白M-T7和Serp-1减轻了大鼠脊髓损伤后的早期炎症。

用抗炎药治疗脊髓损伤（SCI）引发的炎症。我们比较了两种粘液瘤病毒衍生的免疫调节蛋白Serp-1和M-T7与地塞米松（DEX）的局部脊髓或腹膜内输注。SCI引起的出血和坏死是由早期，严重和高度破坏性的炎性巨噬细胞浸润主导的复杂发病机制。我们检查了硬脑膜下持续7天的M-T7（趋化因子调节剂）或Serp-1（纤溶酶原激活剂和因子抑制剂）的输注。成熟的雄性大鼠通过渗透泵将硬膜外球囊压迫性脊髓损伤（SCI），并在硬膜下持续输注Serp-1，M-T7，DEX或生理盐水7天。另一组患有SCI的大鼠进行了腹腔内输注。临床评估包括终点监测体重，出血性膀胱炎和双侧脚趾捏反应。对脊髓的切片进行组织学分析，并通过标准化方案对损伤腔（COI）中的巨噬细胞数进行计数。尽管给予DEX的大鼠表现出明显的体重减轻，脱水和皮肤萎缩，与类固醇毒性相符，但注入Serp-1和M-T7的大鼠没有毒性。Serp-1改善了戒断反应。硬膜下输注Serp-1，M-T7和DEX可显着减少吞噬性CD68阳性巨噬细胞的数量。腹膜内输注仅M-T7减少巨噬细胞计数，Serp-1仅显示趋势。局部注入高活性免疫调节蛋白；Serp-1和M-T7靶向丝氨酸蛋白酶和趋化因子途径，在大鼠模型中出现严重SCI后显示出极好的神经保护潜力，无不良副作用。持续的硬膜下输注为治疗SCI提供了另一种给药途径。