Hanne Nicholas J, Steward Andrew J, Geeroms Carla, Easter Elizabeth D, Gensch Hannah T, Kerckhofs Greet, Parac-Vogt Tatjana N, Sheng Huaxin, Cole Jacqueline H
Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, and North Carolina State University, Raleigh, NC, USA.
Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.
Bone Rep. 2025 Jan 4;24:101824. doi: 10.1016/j.bonr.2025.101824. eCollection 2025 Mar.
Stroke patients lose bone mass and experience fracture at an elevated rate. Although functional intraosseous vasculature is necessary for skeletal maintenance, the effect of stroke on osteovasculature is unknown. In this study we characterized changes to osteovascular perfusion, structure, and composition following mild-to-moderate stroke severity in mice, both with and without exercise therapy. Twelve-week-old male mice ( = 27) received either an ischemic stroke (middle cerebral artery occlusion) or sham procedure, followed by a four-week recovery with either moderate daily treadmill or sedentary activity. Intraosseous perfusion, measured weekly in the proximal tibial metaphysis with laser Doppler flowmetry, was reduced for two weeks in the stroke group relative to the sham group. After four weeks, osteovascular structure was assessed in the distal femoral metaphysis with contrast-enhanced computed tomography. Increased osteovascular volume and branching, decreased number of smaller vessels (6-22 μm), and increased number of larger vessels (>66 μm) were observed in the stroke groups compared to sham groups, which may be a compensatory response to early perfusion deficits. Although moderate exercise mitigated the impact of stroke on osteovascular perfusion and volume, it tended to reduce the amount of osteogenic type H vasculature quantified with immunofluorescence microscopy and, exacerbated by stroke effects, produced fewer vessels in close proximity to bone and thus may have detrimental effects on bone remodeling during early stroke recovery. Since results were similar in both limbs, the effects of ischemic stroke on osteovascular perfusion and structure were primarily systemic, rather than resulting from paresis or disuse, providing new insight for future studies on the pathogenesis and treatment of skeletal fragility in stroke patients.
中风患者骨量流失，骨折发生率升高。尽管功能性骨内血管系统对骨骼维持至关重要，但中风对骨血管系统的影响尚不清楚。在本研究中，我们对轻度至中度中风严重程度的小鼠在接受或未接受运动疗法的情况下，骨血管灌注、结构和组成的变化进行了表征。12周龄雄性小鼠（n = 27）接受缺血性中风（大脑中动脉闭塞）或假手术，随后进行为期四周的恢复，恢复方式为每天适度的跑步机运动或久坐不动。每周用激光多普勒血流仪测量胫骨近端干骺端的骨内灌注，中风组相对于假手术组在两周内骨内灌注降低。四周后，用对比增强计算机断层扫描评估股骨远端干骺端的骨血管结构。与假手术组相比，中风组观察到骨血管体积增加和分支增多，较小血管（6 - 22μm）数量减少，较大血管（>66μm）数量增加，这可能是对早期灌注不足的一种代偿反应。尽管适度运动减轻了中风对骨血管灌注和体积的影响，但它倾向于减少通过免疫荧光显微镜定量的成骨H型血管数量，并且由于中风影响而加剧，在靠近骨骼处产生的血管较少，因此可能在中风早期恢复期间对骨重塑产生不利影响。由于双侧肢体结果相似，缺血性中风对骨血管灌注和结构的影响主要是全身性的，而非由麻痹或废用引起，这为未来研究中风患者骨骼脆弱性的发病机制和治疗提供了新的见解。
