Role Of Bone Blood Flow In Bone Loss Following SCI
骨血流量在 SCI 后骨质流失中的作用
基本信息
- 批准号:9236938
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-10-01 至 2018-09-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimal ModelAnimalsBicyclingBloodBlood VesselsBlood flowBone DensityClinical TrialsConsciousContusionsDataDevelopmentDistalEndotheliumExerciseFemurFluorochromeFoodFood AdditivesFractureGlucocorticoidsHemorrhageHerbHumanInjuryIschemiaLifeLimb structureLocomotor RecoveryMeasuresMechanical StimulationMechanicsMicrospheresMineralsModelingMorphologyMotorMusMusculoskeletalOsteoblastsOsteoclastsOsteogenesisOsteoporosisOsteoporoticPECAM1 geneParalysedPatientsPharmaceutical PreparationsPlayPopulationPostmenopausal OsteoporosisPreventionProtective AgentsRattusReportingRiskRodentRodent ModelRoleSpinal cord injurySpinal cord injury patientsSprague-Dawley RatsStaining methodStainsSurfaceTestingTimeTrainingVascular Endothelial Growth FactorsVascular blood supplyVeteransWorkYarrowbisphosphonatebonebone lossbone massfemoral arteryimprovedin vivoinnovationlimb bonemalemicroCTmouse modelnovel therapeuticspre-clinicalpreclinical studypreventresearch studysham surgeryskeletal
项目摘要
Bone loss following spinal cord injury (SCI) is an important problem in the Veteran population.
Bisphosphonates are currently the frontline therapy for postmenopausal osteoporosis, but do not restore
bone in patients following SCI. Thus there is a need for new therapies. Bone loss following SCI results in
part from disuse, but may also result from a variety of other mechanisms including the loss of blood supply to
the bone. Ding et al. have shown in a mouse model, that SCI causes a dramatic loss of bone vascular
volume. We propose a preclinical rat study to determine 1) whether reduced bone blood and reduced
vascular volume play a role in bone loss following SCI and 2) whether bone loss can be prevented by
administration of tetramethylpyrazine (TMP) alone or in combination with passive motorized bicycle training.
Our proposed study is innovative because 1) we will study bone blood supply comprehensively (i.e. we will
measure both blood flow and vascular volume), 2) we will determine whether bone blood supply is
compromised before SCI-induced loss of bone mineral and 3) we will test strategies to prevent both loss of
bone blood supply and loss of bone mineral following SCI. Our study has 2 specific aims.
Aim 1: Determine whether severe SCI causes early deficits in bone blood flow and bone vascularity and
whether the time course of these changes precedes or matches that of cancellous bone loss. Hypothesis 1:
SCI will cause significant loss of femoral blood flow (via in vivo microsphere administration) and femoral
vascular volume (via micro CT of perfused vasculature) that will precede or accompany the reduced cancellous
bone volume, reduced trabecular number, and increased osteoclast surface that we have previously reported
to occur following SCI.
Aim 2: Determine whether SCI-induced deficits in bone blood flow, bone vascularity, and cancellous bone
volume are prevented by TMP administration or by motorized bicycle training, alone or in combination.
Hypothesis 2: Administration of TMP will prevent SCI-induced changes in vasculature and cancellous bone by
protecting bone blood flow. Motorized bicycle exercise will also partially protect bone as we have previously
observed. We predict that the greatest protection will occur in the group receiving combined TMP and bicycle
straining.
Male Sprague-Dawley rats will receive a severe contusion injury vs. sham surgery. Over 4 weeks, we
will assess bone blood flow in femurs by administration of microspheres to conscious rats via the femoral
artery. We will also assess vascular volume in decalcified femurs of rats perfused with vascular microfil at
the time of sacrifice. We will perform comprehensive analysis of cancellous bone morphology in distal femur,
employing both micro CT and histomorphometry. In addition, fluorochromes will be administered to live
animals to allow for histological assessment of osteoblast and osteoclast surfaces. We will administer multi-
modal therapy (TMP with or without passive motorized bicycle training) to prevent bone loss following SCI.
TMP is an herb-derived agent that is approved as a food additive and has been shown to protect bone
following glucocorticoid administration. Our preliminary data shows that passive bicycle training partially
protects bone following SCI.
脊髓损伤后骨丢失是退伍军人面临的一个重要问题。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Joshua F. Yarrow其他文献
Joshua F. Yarrow的其他文献
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{{ truncateString('Joshua F. Yarrow', 18)}}的其他基金
ShEEP Request for High Resolution Desktop MicroCT System
SheEEP 请求高分辨率桌面 MicroCT 系统
- 批准号:
10538047 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Development and Validation of a Rodent FES Bicycle System
啮齿动物 FES 自行车系统的开发和验证
- 批准号:
10367994 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Development and Validation of a Rodent FES Bicycle System
啮齿动物 FES 自行车系统的开发和验证
- 批准号:
10554098 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Locomotor Training with Anabolic Adjuvants for Musculoskeletal Recovery After SCI
使用合成代谢佐剂进行运动训练以促进 SCI 后的肌肉骨骼恢复
- 批准号:
9505304 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Locomotor Training with Anabolic Adjuvants for Musculoskeletal Recovery After SCI
使用合成代谢佐剂进行运动训练以促进 SCI 后的肌肉骨骼恢复
- 批准号:
10407486 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Locomotor Training with Anabolic Adjuvants for Musculoskeletal Recovery After SCI
使用合成代谢佐剂进行运动训练以促进 SCI 后的肌肉骨骼恢复
- 批准号:
10840774 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI
SCI 后高于替代睾酮加非那雄胺的治疗
- 批准号:
9901435 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI
SCI 后高于替代睾酮加非那雄胺的治疗
- 批准号:
10251014 - 财政年份:2015
- 资助金额:
-- - 项目类别:
In Vivo Microcomputed Tomography (uCT) Acquisition
体内微计算机断层扫描 (uCT) 采集
- 批准号:
8948248 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI
SCI 后高于替代睾酮加非那雄胺的治疗
- 批准号:
10275496 - 财政年份:2015
- 资助金额:
-- - 项目类别:
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