Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury
生酮饮食改善急性脊髓损伤患者神经功能恢复的评价
基本信息
- 批准号:10754456
- 负责人:
- 金额:$ 36.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-09 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AcuteAlternative TherapiesAntiinflammatory EffectApoptoticBiochemicalBiological MarkersBlood GlucoseBlood ProteinsBrainCaloric RestrictionCarbohydratesClinicalClinical TrialsConsumptionDataDietDietary InterventionEvaluationFastingFatty acid glycerol estersFibrinogenForelimbGlucoseGlutamatesHealthHospitalsHumanHyperglycemiaIndividualInflammationInhibition of ApoptosisInjuryInnovative TherapyInsulinInterventionInvestigationKetone BodiesKetosesKetosisLeadLength of StayMetabolicMinorModelingMolecularMotorNeurological outcomeNeuroprotective AgentsNutritionalOutcomePathologicPathway interactionsPatient-Focused OutcomesPatientsPeptidesPersonsPilot ProjectsProcessProteinsQuality of lifeRandomized, Controlled TrialsRattusRecoveryRecovery of FunctionResearchResearch PersonnelRestRodentSamplingSensorySerumSpinal CordSpinal cord injurySpinal cord injury patientsStrokeTestingTimeTranslatingTraumatic Brain InjuryTraumatic injuryUpper Extremityacute careanimal datacostdesigndisabilityexcitotoxicityfunctional independencefunctional outcomesfunctional statusglycemic controlimprovedketogenic dietmortalitymotor recoveryneuroinflammationneurological recoveryneuroprotectionnoveloxidative damagepharmacologicpre-clinicalpreventprimary outcomeprospectiverehabilitation strategytreatment strategy
项目摘要
ABSTRACT
Despite extensive research, clinical advancements, and improved rehabilitation strategies, spinal
cord injury (SCI) continues to be a significant cause of disability and mortality worldwide, and no
pharmacologic therapy has demonstrated significant improvement effects in the neurological or
functional recovery of individuals with SCI. Therefore, there is an urgent need for innovative
therapies for improving neurorecovery after SCI. The scientific premise of this project builds upon
accumulating evidence that diet-based therapies, such as the ketogenic diet (KD), offer effective
neuroprotection against secondary injury cascades and improve forelimb motor function in a rat
model of SCI. The KD is a high-fat, low-carbohydrate diet designed to mimic the metabolic and
biochemical changes that occur during calorie restriction, specifically ketosis. Ketone bodies have
been shown to exert neuroprotective effects by attenuating neuroinflammation and inhibiting
apoptosis in the spinal cord. Because neuroinflammation and induction of apoptotic pathways
lead to progressive degeneration in the spinal cord shortly after the injury, inhibition of these
processes by ketone bodies may enhance neurological recovery after an SCI. Indeed, our recent
pilot study showed for the first time that, compared with a standard hospital diet (SD), 5 weeks of
KD improved upper extremity motor function in patients with acute SCI. In addition, levels of a
neuroinflammatory blood protein, fibrinogen, were lower in the KD serum samples than in the SD
serum samples, suggesting a KD may induce anti-inflammatory effects in part by reducing
fibrinogen. The acute stage after SCI is also characterized by hyperglycemia, which is strongly
associated with poor functional outcomes at discharge. In our pilot study, fasting serum glucose
levels decreased by 24 mg/dl in the KD group but increased by 0.7 mg/dl in the SD group. These
provocative findings have led us to our central hypothesis that SCI patients who consume a KD
over the first 5 weeks (average hospital stay) after injury will have better neurological recovery,
functional independence, and glycemic control than the SCI patients who consume an SD during
this period. We will test this hypothesis in a randomized, controlled trial with two specific aims: 1)
Determine if 5 weeks of KD vs. SD significantly improves motor and sensory function, functional
independence, and glycemic control in patients with acute SCI, and 2) Quantify serum biomarkers
that are responsible for improvements in neurological recovery and functional independence. Our
findings will uncover the molecular mechanisms by which targeted nutritional strategies can
promote neurorecovery shortly after SCI and may lead to a safe, effective, simple, and economical
intervention that improves health outcomes after SCI.
摘要
尽管有广泛的研究,临床上的进步,以及更好的康复策略,脊柱
脊髓损伤(SCI)仍然是全世界残疾和死亡的重要原因,没有
药物治疗已显示出显著的改善神经功能障碍的效果
脊髓损伤患者的功能恢复。因此,迫切需要创新
改善脊髓损伤后神经康复的治疗方法。这个项目的科学前提是建立在
越来越多的证据表明,基于饮食的疗法,如生酮饮食(KD),提供了有效的
对继发性损伤的神经保护级联反应和改善大鼠前肢运动功能
SCI模型。KD是一种高脂肪、低碳水化合物的饮食,旨在模拟新陈代谢和
在卡路里限制期间发生的生化变化,特别是酮症。酮体有
已被证明通过减轻神经炎症和抑制发挥神经保护作用
脊髓中的细胞凋亡。因为神经炎症和诱导细胞凋亡的途径
导致损伤后不久脊髓进行性退化,抑制这些
酮体的作用可能促进脊髓损伤后神经功能的恢复。事实上,我们最近
初步研究首次表明,与标准医院饮食(SD)相比,5周的
KD能改善急性脊髓损伤患者的上肢运动功能。此外,
KD患者血清中神经炎性血蛋白、纤维蛋白原低于SD患者
血清样本,提示KD可能部分通过减少
纤维蛋白原。脊髓损伤后的急性期也以高血糖为特征,这是强烈的
与出院时不良的功能结局有关。在我们的初步研究中,空腹血糖
KD组降低24 mg/dl,SD组升高0.7 mg/dl。这些
挑衅性的发现将我们引向了我们的中心假设,即使用KD的脊髓损伤患者
在受伤后的前5周(平均住院时间),神经恢复会更好,
与服用SD的脊髓损伤患者相比,功能独立性和血糖控制更好
这段时间。我们将在一项随机对照试验中检验这一假设,目的有两个:1)
确定KD与SD的5周是否显著改善了运动和感觉功能、功能
急性脊髓损伤患者的独立性和血糖控制,以及2)定量血清生物标记物
对改善神经恢复和功能独立性负责。我们的
研究结果将揭示靶向营养策略可以
促进脊髓损伤后不久的神经康复,并可能导致安全、有效、简单和经济的
改善脊髓损伤后健康结局的干预措施。
项目成果
期刊论文数量(2)
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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Ceren Yarar-Fisher的其他文献
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{{ truncateString('Ceren Yarar-Fisher', 18)}}的其他基金
Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals with Acute Spinal Cord Injury
生酮饮食改善急性脊髓损伤患者神经功能恢复的评价
- 批准号:
10375524 - 财政年份:2019
- 资助金额:
$ 36.66万 - 项目类别:
Targeting skeletal muscle to improve metabolic health in individuals with spinal cord injury
针对骨骼肌改善脊髓损伤患者的代谢健康
- 批准号:
10214648 - 财政年份:2017
- 资助金额:
$ 36.66万 - 项目类别:
Targeting skeletal muscle to improve metabolic health in individuals with spinal cord injury
针对骨骼肌改善脊髓损伤患者的代谢健康
- 批准号:
9242479 - 财政年份:2017
- 资助金额:
$ 36.66万 - 项目类别:
Targeting skeletal muscle to improve metabolic health in individuals with spinal cord injury
针对骨骼肌改善脊髓损伤患者的代谢健康
- 批准号:
9527852 - 财政年份:2017
- 资助金额:
$ 36.66万 - 项目类别:
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