REHABILITATION OF MICRONEUROVASCULAR GRAFTS IN OLD RATS

候选人的描述--丽莎M。拉金获得了博士学位。从 1993年1月毕业于加州戴维斯大学，主修 营养学和新陈代谢，辅修神经生理学。 博士学位 博士论文涉及研究衰老对骨骼肌的影响 葡萄糖代谢 她的主要研究兴趣是衰老的影响 对骨骼肌代谢的影响 这位候选人在过去的三年里 在老年学研究所完成博士后研究 在密歇根大学，她继续研究 年龄对骨骼肌代谢功能的影响。 协同 博士候选人约翰·福克纳调查了 骨骼肌代谢，这可以解释观察到的降低 移植肌肉的功能。 候选人未来的研究 目标是开发新的专业知识，并应用从 这些肌肉移植来研究衰老的能力 移植肌肉以在外科手术后恢复。 这位Mrsda将 允许候选人继续她的职业发展， 作为一名独立调查员，她对年龄有着独特的理解- 在骨骼肌代谢和在战神的相关变化， 肌肉收缩力学，肌肉微神经血管移植， 再生，和慢性电刺激，这是至关重要的， 肌内微神经血管移植后康复成功。 环境描述--丽莎博士M.拉金将有权访问 三名导师和两名顾问的专业知识和设施， 这一建议的巨大成功：哈尔特博士（葡萄糖代谢和衰老）， 博士Faulkner（肌肉力学和衰老），Supiano博士（肾上腺素能受体 功能和衰老），Kuzon博士（功能和代谢特征， 肌肉移植）和Galecki博士（生物统计学家）。 进一步的援助和 教育机会将由学院的教师提供 克劳德·佩珀老年美国人独立中心（Claude Pepper Older Americans Independence Center） 密歇根大学为老年啮齿动物提供核心设施 （CFAR）。 此外，候选人将有机会获得教师和 老年医学研究，教育，临床中心，VAMC的设施。 研究描述--神经血管移植可能是一种 潜在的强大的方法，用于恢复肌肉功能， 在老年人群中经常发现的情况下功能丧失， 局部肌肉或神经损伤，切除恶性肿瘤的手术， 中风或中枢和周围神经系统疾病。 虽然 大部分形态和生理特征恢复到 整个骨骼肌移植后的基线，随后 比力和抗疲劳性的恢复受损。 的 移植的肌肉不能达到特定的前屈和抵抗力， 疲劳损害了移植手术在修复中的有效性 肌肉功能障碍 此外，老龄化还与 骨骼肌强度和抗疲劳性。 确定 导致强度和耐久性降低的机制 老化和/或移植的骨骼肌可以帮助预防， 老年人骨骼肌疾病的治疗。 这项拟议的研究 将使用内侧腓肠肌原位微神经血管移植 (MGN)肌肉作为模型，以检查衰老大鼠的能力， 在整个肌肉移植手术后维持动力，并确定 如果维持功率的能力的预期降低是由于 失神经肌肉纤维数量增加，导致 移植肌肉的代谢能力。 此外，拟议的研究 将检查慢性低频电的有效性 刺激作为促进衰老MGN康复干预 微神经血管移植手术后的肌肉

Description of the candidate --Lisa M. Larkin obtained a Ph.D. from the University of California, Davis in January 1993 where she majored in Nutrition and metabolism and minored in Neurophysiology. Her Ph.D. dissertation involved studies on the effect of aging on skeletal muscle glucose metabolism. Her primary research interest is the effect of aging on skeletal muscle metabolism. The candidate has spent the last three years completing a postdoctoral fellowship in the institute of Gerontology at the University of Michigan where she continued to investigate the effect of age on the metabolic function of skeletal muscle. In collaboration with Dr. John Faulkner, the candidate investigated post-surgical alterations in skeletal muscle metabolism which could explain the observed decreased functional ability of the grafted muscle. The candidate's future research goal is to develop new expertise and to apply the knowledge obtained from these young-grafted muscles to investigate the ability for senescent- grafted muscle to rehabilitate after surgical procedures. This MRSDA will allow the candidate to continue her career development by establishing herself as an independent investigator with unique understanding of age- related changes both in skeletal muscle metabolism and in the ares of muscle contractile mechanics, muscle microneurovascular grafting and regeneration, and chronic electrical stimulation which are critical to successful rehabilitation after microneurovascular grafting in muscle. Description of the environment -- Dr. Lisa M. Larkin will have access to the expertise and facilities of three mentors and two consultant to ensure athe success of this proposal: Dr. Halter (glucose metabolism and aging), Dr. Faulkner (muscle mechanics and aging), Dr. Supiano (adrenergic receptor function and aging), Dr. Kuzon (functional and metabolic characteristics in muscle grafts), and Dr. Galecki (biostatistician). Further assistance and educational opportunities will be provided by the faculty of the Institute of Gerontology and the Claude Pepper Older Americans Independence Center at the University of michigan which maintain a Core facility for Aged Rodents (CFAR). In addition, the candidate will have access to the faculty and facilities of the Geriatric Research, Education, Clinical Center, VAMC. Description of the research -- Microneurovascular grafting could be a potentially powerful method for th restoration of muscle function following loss of function in condition often found in the aging population such a regional muscle or nerve injury, surgery to remove malignant tumors, stroke, or central and peripheral nervous system disorders. Although the majority of morphological and physiological characteristics return to baseline following the grafting of whole skeletal muscle, subsequent restoration of specific force and resistance to fatigue is impaired. The inability of grafted muscle to achieve the specific fore and resistance to fatigue compromises the usefulness of the grafting procedure in the repair of muscle dysfunction. In addition, aging is associated with a decline in skeletal muscle strength and the resistance to fatigue. Determining the mechanism(s) responsible for the decrease in strength and endurance of aging and/or grafted skeletal muscle could help in the prevention and treatment of skeletal muscle disorders in the elderly. This proposed study will use an orthotopic microneurovascular graft of the medial gastrocnemius (MGN) muscle as a model to the examine the ability of senescent rats to sustain power following a whole muscle grafting procedure and to determine if the expected decrease in the ability to sustain power is due to an increased number of denervated muscle fibers, resulting in diminished metabolic capacity in the grafted muscle. In addition, the proposed study will examine the effectiveness of chronic low frequency electrical stimulation as an intervention to enhance rehabilitation of senescent MGN muscle from a microneurovascular grafting procedure.