Treatment of Functional Deficits IN tongue muscles induced by radiation and chemoradiation treatment

摘要 头颈部癌症治疗的放射治疗和化疗使正常组织暴露在辐射下， 这有许多破坏性的影响，并经常导致沟通和吞咽困难。而当 肌肉无力和纤维化可能是严重沟通障碍和吞咽障碍的原因 辐射后的功能，对体内潜在的生物变化进行的研究很少 辐射后头部和颈部的肌肉，或这些持久的负面影响的可能治疗方法。 骨骼肌可以在多个层次的结构和功能上适应不断变化的需求。运动训练 或通过神经肌肉电刺激(NMES)增强肌肉收缩 有利于预防或逆转肌肉组织损伤。然而，检查这些的对照研究 尚未实现推定的惠益，也未确定最佳治疗模式。我们的 假设放疗和放化疗导致的语言和吞咽功能下降是 很大程度上是由于舌肌结构和功能的改变。此外，我们假设舌头 运动或NMES将导致舌外肌肉的表型变化，这将改善舌头 肌肉功能。为了检查这些与临床相关的问题，我们将使用老鼠模型来测试两种不同的 治疗放疗和放化疗的舌疗范例(舌操；NMES)- 导致肌肉损伤。这项拟议的研究有两个具体目标：1)确定如何治疗 形态影响放化疗中的形态、生化和生理变化-- 诱导的舌肌损伤，2)发现舌头运动和/或NMES治疗如何影响 放化疗后吞咽的功能测量。这项工作具有创新性和创新性。 重要的是因为舌头运动或NMES可以预防或治疗 放射或化疗引起的沟通和吞咽功能障碍在很大程度上还没有被探索过。我们的 动物模型和治疗方法类似于用于人类患者的治疗方法，并遵循 增加翻译概率的医学指南。此外，这项工作对于提供一种 了解潜在的放射治疗干预机制的基础--和 放化疗引起的颅骨损伤。调查结果的翻译将有助于增加 放疗和放化疗所致舌肌损伤的治疗效果 在头颈癌患者中很常见。

ABSTRACT Radiotherapy and chemoradiation for head and neck cancer treatment exposes normal tissues to radiation, which has many devastating effects and often results in difficulty with communication and swallowing. While muscle weakness and fibrosis are possible etiologies for disruptions in critical communicative and deglutition functions following radiation, very little research has been performed on underlying biological changes within muscles of the head and neck following radiation, or possible treatments for these lasting negative effects. Skeletal muscles can adapt at multiple levels of structure and function to changing demands. Exercise training of the tongue, or enhanced muscle contraction via neuromuscular electrical stimulation (NMES) may be beneficial for preventing or reversing muscle tissue damage. However, controlled research examining these putative benefits has not been performed and optimal treatment modalities have not been established. Our hypothesis is that radiotherapy and chemoradiation-induced decline in speech and swallowing function is largely due to alterations in tongue muscle structure and function. Further, we hypothesize that tongue exercise or NMES will result in phenotypic changes in extrinsic tongue muscles that will improve tongue muscle function. To examine these clinically-relevant issues, we will use a rat model to test two different tongue treatment paradigms (tongue exercise; NMES) for remediation of radiotherapy and chemoradiation- induced muscle damage. The proposed research has two specific aims: 1) To determine how treatment modality affects morphological, biochemical, and physiological changes in radiotherapy and chemoradiation- induced muscle damage of the tongue, 2) To discover how tongue exercise and/or NMES treatment affects functional measures of deglutition following radiotherapy/chemoradiation. This work is innovative and significant because the mechanisms by which tongue exercise or NMES can prevent or treat the effects of radiation- or chemoradiation-induced communication and swallowing dysfunction is largely unexplored. Our animal model and treatments are analogs to treatments used in human patients and follow the Institute of Medicine guidelines for increasing probability of translation. Further, this work is highly significant in providing a basis for understanding the mechanisms underlying the potential of therapeutic interventions for radiation- and chemoradiation-induced cranial impairments. Translation of findings will assist with increasing the effectiveness of treatments for radiation- and chemoradiation-induced tongue muscle impairments that are so prevalent in patients with head and neck cancer.