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

摘要 头颈部癌症的放射治疗和化学放射治疗使正常组织暴露于辐射， 这具有许多破坏性的影响，并且经常导致交流和吞咽困难。而 肌无力和纤维化可能是关键性交流和吞咽功能中断的病因 辐射后的功能，很少有研究已经进行了内在的生物变化 头部和颈部肌肉的辐射，或可能的治疗这些持久的负面影响。 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， 有益于预防或逆转肌肉组织损伤。然而，对照研究检查这些 假定的益处尚未实现，最佳治疗模式尚未确立。我们 有一种假说认为，放疗和放化疗引起的语言和吞咽功能下降， 主要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将导致外在舌肌的表型变化， 肌肉功能为了研究这些临床相关的问题，我们将使用大鼠模型来测试两种不同的 舌治疗范例（舌运动; NMES）用于放疗和放化疗的补救- 导致肌肉损伤。这项研究有两个具体目标：1）确定如何治疗 形态影响放疗和放化疗中的形态、生化和生理变化， 2）为了发现舌头运动和/或NMES治疗如何影响 放疗/放化疗后吞咽功能测量。这项工作具有创新性， 意义重大，因为舌头运动或NMES可以预防或治疗 放射或化学放射诱导的交流和吞咽功能障碍在很大程度上是未探索的。我们 动物模型和治疗类似于人类患者中使用的治疗，并遵循美国医学会 增加翻译可能性的医学指南。此外，这项工作在提供一个 理解放射治疗干预潜力的机制的基础- 放化疗引起的脑损伤调查结果的翻译将有助于增加 治疗放射和化学放射引起的舌肌损伤的有效性， 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.