Hanne Nicholas J, Steward Andrew J, Sessions Marci R, Thornburg Hannah L, Sheng Huaxin, Cole Jacqueline H
Joint Department of Biomedical Engineering, University of North Carolina-Chapel Hill and North Carolina State University, 4130 Engineering Building III, Campus, Box 7115, Raleigh, NC 27695.
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710.
J Biomech Eng. 2019 Dec 1;141(12):121008-121008-13. doi: 10.1115/1.4045113.
Ischemic stroke induces rapid loss in bone mineral density that is up to 13 times greater than during normal aging, leading to a markedly increased risk of fracture. Little is known about skeletal changes following stroke beyond density loss. In this study, we use a mild-moderate middle cerebral artery occlusion model to determine the effects of ischemic stroke without bedrest on bone microstructure, dynamic bone formation, and tissue composition. Twenty-seven 12-week-old male C57Bl/6J mice received either a stroke or sham surgery and then either received daily treadmill exercise or remained sedentary for 4 weeks. All mice were ambulatory immediately following stroke, and limb coordination during treadmill exercise was unaffected by stroke, indicating similar mechanical loading across limbs for both stroke and sham groups. Stroke did not directly detriment microstructure, but exercise only stimulated adaptation in the sham group, not the stroke group, with increased bone volume fraction and trabecular thickness in the sham distal femoral metaphysis. Stroke differentially decreased cortical area in the distal femoral metaphysis for the affected limb relative to the unaffected limb, as well as endosteal bone formation rate in the affected tibial diaphysis. Although exercise failed to improve bone microstructure following stroke, exercise increased mineral-to-matrix content in stroke but not sham. Together, these results show that stroke inhibits exercise-induced changes to femoral microstructure but not tibial composition, even without changes to gait. Similarly, affected-unaffected limb differences in cortical bone structure and bone formation rate in ambulatory mice show that stroke affects bone health even without bedrest.
缺血性中风会导致骨矿物质密度迅速下降，其下降幅度比正常衰老过程中高出多达13倍，从而显著增加骨折风险。除了密度损失外，关于中风后骨骼变化的了解甚少。在本研究中，我们使用轻度至中度大脑中动脉闭塞模型来确定无卧床休息的缺血性中风对骨微结构、动态骨形成和组织组成的影响。27只12周龄雄性C57Bl/6J小鼠接受中风手术或假手术，然后要么每天进行跑步机运动，要么持续久坐4周。所有小鼠在中风后立即能够行走，并且跑步机运动期间的肢体协调性不受中风影响，这表明中风组和假手术组的肢体机械负荷相似。中风并未直接损害微结构，但运动仅在假手术组而非中风组中刺激了适应性变化，假手术组股骨远端干骺端的骨体积分数和小梁厚度增加。相对于未受影响的肢体，中风使受影响肢体的股骨远端干骺端皮质面积差异减小，同时受影响胫骨骨干的骨内膜骨形成率也降低。尽管中风后运动未能改善骨微结构，但运动增加了中风组而非假手术组的矿物质与基质含量。总之，这些结果表明，即使在不改变步态的情况下，中风也会抑制运动诱导的股骨微结构变化，但不会抑制胫骨组成的变化。同样，在能行走的小鼠中，受影响肢体与未受影响肢体在皮质骨结构和骨形成率上的差异表明，即使没有卧床休息，中风也会影响骨骼健康。
