REHABILITATION OF MICRONEUROVASCULAR GRAFTS IN OLD RATS

候选人描述--丽莎·M·拉金从 1993年1月，她在加州大学戴维斯分校主修 营养与新陈代谢，辅修神经生理学。她的博士学位。 论文涉及衰老对骨骼肌影响的研究。 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 年在老年学研究所完成博士后奖学金 在密歇根大学，她继续研究这种影响 年龄对骨骼肌代谢功能的影响。与 约翰·福克纳博士，这位候选人研究了手术后的变化 可以解释观察到的下降的骨骼肌代谢 移植肌肉的功能能力。候选人未来的研究 目标是开发新的专业知识并应用从以下方面获得的知识 这些年轻的移植肌肉来研究衰老的能力- 移植的肌肉在手术后进行康复。这个MRSDA将 允许应聘者通过建立 作为一名独立调查员，她对年龄有着独特的理解- 与此相关的骨骼肌代谢变化和腹主动脉 肌肉收缩力学，肌肉微神经血管移植和 再生和慢性电刺激，这对 肌肉内微神经血管移植术后康复成功。 环境描述--丽莎·M·拉金博士将有权 三名导师和两名顾问的专业知识和设施，以确保 这项提议的成功：哈尔特博士(葡萄糖代谢和衰老)， 福克纳博士(肌肉力学和衰老)，苏皮亚诺博士(肾上腺素能受体) 功能和衰老)，Kuzon博士( 肌肉移植)和Galecki博士(生物统计学家)。进一步的援助和 学院的教职员工将提供教育机会 老年学和克劳德·佩珀老年美国人独立中心 密歇根大学为老年啮齿动物提供核心设施 (CFAR)。此外，候选人将有权接触教职员工和 VAMC老年病研究、教育、临床中心的设施。 研究描述--微神经血管移植可能是一种 术后肌肉功能恢复的潜在有效方法 在老龄化人口中经常出现的功能丧失的情况，如 局部肌肉或神经损伤，切除恶性肿瘤的手术， 中风，或中枢和外周神经系统疾病。尽管 大多数形态和生理特征恢复到 整个骨骼肌移植后的基线，随后 比力和抗疲劳能力的恢复受到损害。这个 移植的肌肉不能达到特定的前锋和抵抗 疲劳影响了移植手术在修复过程中的有效性 肌肉功能障碍。此外，衰老与年龄的下降有关。 骨骼肌力量和抗疲劳能力。确定 造成运动员力量和耐力下降的机制(S) 衰老和/或移植的骨骼肌可以帮助预防和 老年人骨骼肌病的治疗。这项拟议的研究 将使用原位腓肠肌内侧微血管移植物 以(MGN)肌肉为模型考察衰老大鼠的运动能力 在整个肌肉移植手术后维持力量，并确定 如果预期的电力维持能力下降是由于 失神经肌肉纤维的数量增加，导致减少 移植肌肉的代谢能力。此外，拟议的研究 将检查慢性低频电疗法的有效性 以刺激为干预手段促进老年性中老年肾炎的康复 来自微神经血管移植手术的肌肉。

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.