Multiple Sessions of Regenerative Electrical Stimulation to Accelerate Sensory Neuron Regeneration

多次再生电刺激加速感觉神经元再生

• 批准号: 10670220
• 负责人: BRIAN BALOG
• 金额: $ 6.86万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670220
• 关键词: Acceleration; Affect; Afferent Neurons; Anatomy; Animals; Brain-Derived Neurotrophic Factor; Clinical; Collaborations; Disease; Electric Stimulation; Evaluation; Faculty; Fellowship; Filament; Galanin; Genes; Growth Associated Protein 43; Hour; Injury; Investigation; Knockout Mice; Knowledge; LIF gene; Laboratories; Learning; Length; Measures; Motor; Motor Neurons; Natural regeneration; Nerve Growth Factors; Nerve Regeneration; Neuroglia; Neurons; Neurosciences; Peripheral Nerves; Peripheral nerve injury; Positioning Attribute; Postdoctoral Fellow; Recovery; Recovery of Function; Regimen; Sensory; Spinal Ganglia; Techniques; Testing; Time; Woman; Work; afferent nerve; brain-derived growth factor; career; injured; men; motor function recovery; mouse model; neuron regeneration; neurotrophic factor; painful neuropathy; peripheral nerve regeneration; pre-clinical; preclinical study; regenerative; sciatic nerve; sciatic nerve injury; skills; success

Project Summary Peripheral nerve injuries (PNIs) affect men and women in the prime of their lives, with the loss of motor and sensory function and neuropathic pain. Regenerative electrical stimulation has been shown to accelerate functional recovery after a PNI. Preclinical studies have shown that multiple one-hour sessions of regenerative promoting electrical stimulation can further accelerate motor function recovery, but have a detrimental effect on sensory regeneration. An investigation to determine a set of parameters that would benefit both motor and sensory is needed so multiple regenerative stimulation sessions can become a possible treatment. To evaluate different lengths of stimulation sessions, a few regenerative associated genes will be evaluated: galanin (GAL), LIF, and GAP 43, but previous studies have not evaluated GAL or LIF after electrical stimulation treatment. I hypothesize that decreasing the length of the stimulation will allow for increasing the number of stimulation sessions while still allowing enhanced LIF and GAL expression. To assess this, I will determine if LIF and GAL are down- regulated after three hours of regenerative promoting electrical stimulation after a unilateral sciatic nerve injury; if so, LIF and GAL with GAP 43 will be used to determine a set of parameters for multiple stimulation session that promote sensory nerve regeneration. The expression will be determined via the RNAscope of LIF, GAL, and GAP 43, a technique I will learn from the Zigmond laboratory. The parameters found will then be used to determine if they accelerate regeneration. Regeneration will be assessed via von Fray filaments, another technique I will learn from the Zigmond lab.

项目概要 周围神经损伤 (PNI) 影响正值壮年的男性和女性，导致丧失 运动和感觉功能以及神经性疼痛。再生电刺激已被证明 加速 PNI 后的功能恢复。临床前研究表明，多次一小时 促进再生的电刺激可以进一步加速运动功能的恢复， 但对感觉再生有不利影响。确定一组参数的调查 这对运动和感觉都有好处，所以需要多次再生刺激课程 成为一种可能的治疗方法。为了评估不同长度的刺激过程，一些再生 将评估相关基因：甘丙肽（GAL）、LIF和GAP 43，但之前的研究尚未 电刺激治疗后评估 GAL 或 LIF。我假设减少长度 刺激将允许增加刺激次数，同时仍然允许 增强 LIF 和 GAL 表达。为了评估这一点，我将确定 LIF 和 GAL 是否已关闭 - 单侧坐骨神经后三小时的再生促进电刺激后调节 受伤;如果是这样，LIF 和 GAL 以及 GAP 43 将用于确定多个参数的一组参数 促进感觉神经再生的刺激课程。表达式将通过以下方式确定 LIF、GAL 和 GAP 43 的 RNAscope，这是我将从 Zigmond 实验室学习的一项技术。这 然后，找到的参数将用于确定它们是否加速再生。再生将是 通过冯·弗雷丝进行评估，这是我将从齐格蒙德实验室学到的另一种技术。