Background The permeability of the blood-spinal cord barrier (BSCB) is mainly determined by junction complexes between adjacent endothelial cells (ECs), including tight junctions (TJs) and adherens junctions (AJs), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinases (MMPs) leads to inflammation, neurotoxin production, and neuronal apoptosis. The failure of new blood vessels to effectively regenerate is also an important cause of delayed recovery after SCI. For the first time, we introduced water treadmill training (TT) to help SCI rats successfully exercise and measured the effects of TT in promoting recovery after SCI and the possible mechanisms involved. Methods Sprague-Dawley (200–250 g) rats were randomly divided into the following three groups: sham operated, SCI, and SCI + TT. Animals were sacrificed at 7 or 14 days post-surgery. The degree of neurological deficit, tissue morphology and BSCB permeability were assessed by the Basso-Beattie-Bresnahan (BBB) motor function scale and appropriate staining protocols, and apoptosis, protein expression and vascular EC ultrastructure were assessed by TUNEL staining, Western blotting, immunofluorescence and transmission electron microscopy (TEM). Results Our experiments showed that TT reduced permeability of the BSCB and decreased structural tissue damage. TT significantly improved functional recovery when compared with that in the SCI group; TJ and AJ proteins expression increased significantly after TT, and training reduced apoptosis induced by SCI. TT could promote angiogenesis, and MMP-2 and MMP-9 expression was significantly inhibited by TT. Conclusions The results of this study indicate that TT promotes functional recovery for the following reasons: TT (1) protects residual BSCB structure from further damage, (2) promotes vascular regeneration, and (3) inhibits MMP-2/9 expression to mitigate BSCB damage.

中文翻译：

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水上跑步机训练通过促进血管生成和抑制脊髓损伤后基质金属蛋白酶 2/9 的表达来减轻大鼠血-脊髓屏障的破坏

背景血脊髓屏障（BSCB）的通透性主要由相邻内皮细胞（EC）之间的连接复合物决定，包括紧密连接（TJ）和粘附连接（AJ），脊髓损伤后这些连接复合物会受到严重破坏。 SCI）。运动训练是公认的治疗 SCI 的方法。由基质金属蛋白酶 (MMP) 介导的 BSCB 破坏导致炎症、神经毒素产生和神经元凋亡。新血管无法有效再生也是导致SCI后恢复延迟的重要原因。我们首次引入了水上跑步机训练 (TT) 来帮助 SCI 大鼠成功锻炼，并测量了 TT 在促进 SCI 后恢复的作用及其可能的机制。方法 Sprague-Dawley（200-250 g）大鼠随机分为以下三组：假手术组、SCI组和SCI+TT组。在手术后 7 或 14 天处死动物。通过 Basso-Beattie-Bresnahan (BBB) 运动功能量表和适当的染色方案评估神经功能缺损程度、组织形态和 BSCB 通透性，并通过 TUNEL 染色、蛋白质印迹、免疫荧光评估细胞凋亡、蛋白质表达和血管 EC 超微结构和透射电子显微镜（TEM）。结果 我们的实验表明，TT 降低了 BSCB 的通透性并减少了结构组织损伤。与SCI组相比，TT显着改善了功能恢复；TT后TJ和AJ蛋白表达显着增加，训练减少了SCI诱导的细胞凋亡。TT可以促进血管生成，TT显着抑制MMP-2和MMP-9的表达。结论 本研究结果表明，TT促进功能恢复的原因如下：TT（1）保护残留的BSCB结构免受进一步损伤，（2）促进血管再生，以及（3）抑制MMP-2/9表达以减轻BSCB损害。