Water treadmill training attenuates blood-spinal cord barrier disruption in rats by promoting angiogenesis and inhibiting matrix metalloproteinase-2/9 expression following spinal cord injury

• Main Authors: Xinwang Ying, Qingfeng Xie, Shengcun Li, Xiaolan Yu, Kecheng Zhou, Jingjing Yue, Xiaolong Chen, Wenzhan Tu, Guanhu Yang, Songhe Jiang
• Format: Article
• Language: English
• Published: BMC 2020-11-01
• Series: Fluids and Barriers of the CNS
• Subjects: Spinal cord injury; Blood-spinal cord barrier; Water treadmill training; Vascular regeneration; Matrix metalloproteinase-2/9
• Online Access: https://doi.org/10.1186/s12987-020-00232-1

Abstract 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.