Behavioral and molecular responses to high-intensity exercise in humans with iSCI

iSCI 人类对高强度运动的行为和分子反应

• 批准号: 8595139
• 负责人: Kristan A. Leech
• 金额: $ 3.53万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8595139
• 关键词: Achievement; Acute; Affect; Animal Model; Behavior; Behavioral; Biological Preservation; Brain-Derived Neurotrophic Factor; Cell physiology; Chronic; Development; Dose; Dyskinetic syndrome; Esthesia; Exercise; Exertion; Experimental Designs; Gait; Goals; Human; Impairment; Intervention; Joints; Knowledge; Lead; Locomotion; Locomotor Recovery; Long-Term Effects; Measurement; Measures; Mediating; Metabolic; Molecular; Motor; Movement; Muscle; Nervous System Trauma; Neurologic; Neuromodulator; Neuronal Plasticity; Neurons; Neurosciences; Output; Pathway interactions; Patients; Pattern; Performance; Peripheral; Placebos; Population; Procedures; Process; Production; Proteins; Protocols documentation; Recovery; Recovery of Function; Regimen; Rehabilitation therapy; Reporting; Research; Research Personnel; Role; Serotonin; Serum; Signal Transduction; Spastic; Specificity; Speed; Spinal; Spinal Cord; Spinal cord injury; Training; Venous; Walking; Work; base; experimental analysis; functional improvement; improved; inhibitor/antagonist; intervention effect; kinematics; locomotor tasks; neurotrophic factor; public health relevance; receptor; response; reuptake; technical writing

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in profound impairments in strength and sensation which can lead to the loss of independent mobility and decreased participation in daily activities. Following incomplete SCI, a primary goal of many patients is to regain independent walking ability. Both task specificity and amount of practice are known to have critical roles in the efficacy of locomotor recovery-based interventions after neurological injury. A significant intervention parameter that has yet to be thoroughly explored in humans with neurological injury is the intensity, or power output, of locomotor-based interventions. Studies in animal models of SCI have demonstrated that high-intensity locomotor practice results in an increased expression of neurotrophic factors, improved neuronal connectivity, and the recovery of stepping. Furthermore, the production of neurotrophic factors has also been suggested to be influenced by the neuromodulator serotonin. These findings suggest that locomotor intensity and serotonin signaling in spinal circuitry may be manipulated to potentiate neural plasticity and improve recovery of functional movement following SCI, although rigorous examination of intensity-related effects has not yet been conducted in humans. A previous limitation to the performance of high-intensity exercise regimens in neurological populations is the notion that such activities will lead to increased spastic motor behaviors and result in abnormal movement patterns. However, the acute and chronic effects of intensity on locomotor performance have yet to be well characterized. Therefore, the proposed aims will fill this gap in knowledge and evaluate the effects of locomotor exercise intensity on behavioral and molecular parameters, in addition to the effect of serotonin on the latter. This wil be achieved through the measurement of joint kinematics, coordination, muscle activity, metabolic activity, and serum levels of neurotrophic factors during a graded-intensity locomotor paradigm. The measurements will be collected under baseline conditions, following chronic high-intensity training, and again while exercise is paired with acute pharmacological manipulation of serotonin levels. This information will improve our understanding of the effect of intervention intensity in humans with incomplete SCI. In particular, it will clarify the acute and long-term effects of intervention intensity and elucidate a potential underlying cellular mechanism for these effects. Finally, it will further delineate the intervention parameters that maximize functional recovery, and promote the development of the most effective rehabilitation interventions following neurological injury.

描述（由申请人提供）：脊髓损伤（SCI）导致力量和感觉的严重损伤，可能导致独立行动能力的丧失和日常活动的参与减少。不完全性脊髓损伤后，许多患者的主要目标是恢复独立行走能力。任务的特殊性和练习的量都是