RT Journal Article
SR Electronic
T1 Ischemic Stroke Reduces Bone Perfusion and Alters Osteovascular Structure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 729632
DO 10.1101/729632
A1 Nicholas J. Hanne
A1 Andrew J. Steward
A1 Carla Geeroms
A1 Elizabeth D. Easter
A1 Hannah L. Thornburg
A1 Greet Kerckhofs
A1 Tatjana Parac-Vogt
A1 Huaxin Sheng
A1 Jacqueline H. Cole
YR 2019
UL http://biorxiv.org/content/early/2019/08/08/729632.abstract
AB Rationale 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.Objective To characterize changes to osteovascular function, structure, and composition following mild-to-moderate-severity ischemic stroke in mice, both with and without exercise therapy.Methods and Results Twelve-week-old male mice (n=27) received either a stroke (middle cerebral artery occlusion) or sham procedure, followed by four weeks of daily treadmill or sedentary activity. Intraosseous perfusion, measured weekly in the proximal tibial metaphysis, was reduced by stroke for two weeks. In the second week of recovery, exercise nearly restored perfusion to sham levels, and perfusion tended to be lower in the stroke-affected limb. At the conclusion of the study, osteovascular structure was assessed with contrast-enhanced computed tomography in the distal femoral metaphysis. Stroke significantly increased osteovascular volume and branching but reduced the relative number of blood vessels close to bone surfaces (6-22 µm away) and increased the relative number more than 52 µm away. These differences in vessel proximity to bone were driven by changes in the stroke-exercise group, indicating compounded effects of stroke and exercise. Exercise, but not stroke, nearly reduced the amount of osteogenic Type H blood vessels in the proximal tibial metaphysis, quantified with immunofluorescence microscopy.Conclusions This study is the first to examine the effects of stroke on osteovasculature. Stroke increased the amount of osteovasculature, but since blood vessels close to bone are associated with bone remodeling, the shift in osteovascular structure could play a role in bone loss following stroke. The exercise-induced reduction in the amount of Type H vessels and the stroke-exercise effect on osteovascular structure suggest moderate aerobic activity may have detrimental effects on bone remodeling during early stroke recovery.Ad.DAdipocyte densityAd.ThAdipocyte thicknessAd.V/Ma.VAdipocyte volume per marrow volumeEMCNEndomucinLDFLaser Doppler flowmetryVes.DBlood vessel densityVes.ThBlood vessel thicknessVes.S-BSVessel surface to bone surface distanceVes.V/Ma.VVessel volume per marrow volume