Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
Center for Respiratory Research and Rehabilitation, Department of Physical Therapy and McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA.
Respir Physiol Neurobiol. 2019 Jul;265:19-23. doi: 10.1016/j.resp.2019.01.004. Epub 2019 Jan 11.
Acute intermittent hypoxia (AIH) elicits distinct mechanisms of phrenic motor plasticity initiated by brainstem neural network activation versus local (spinal) tissue hypoxia. With moderate AIH (mAIH), hypoxemia activates the carotid body chemoreceptors and (subsequently) brainstem neural networks associated with the peripheral chemoreflex, including medullary raphe serotonergic neurons. Serotonin release and receptor activation in the phrenic motor nucleus then elicits phrenic long-term facilitation (pLTF). This mechanism is independent of tissue hypoxia, since electrical carotid sinus nerve stimulation elicits similar serotonin-dependent pLTF. In striking contrast, severe AIH (sAIH) evokes a spinal adenosine-dependent, serotonin-independent mechanism of pLTF. Spinal tissue hypoxia per se is the likely cause of sAIH-induced pLTF, since local tissue hypoxia elicits extracellular adenosine accumulation. Thus, any physiological condition exacerbating spinal tissue hypoxia is expected to shift the balance towards adenosinergic pLTF. However, since these mechanisms compete for dominance due to mutual cross-talk inhibition, the transition from serotonin to adenosine dominant pLTF is rather abrupt. Any factor that compromises spinal cord circulation will limit oxygen availability in spinal cord tissue, favoring a shift in the balance towards adenosinergic mechanisms. Such shifts may arise experimentally from treatments such as carotid denervation, or spontaneous hypotension or anemia. Many neurological disorders, such as spinal cord injury or stroke compromise local circulatory control, potentially modulating tissue oxygen, adenosine levels and, thus, phrenic motor plasticity. In this brief review, we discuss the concept that local (spinal) circulatory control and/or oxygen delivery regulates the relative contributions of distinct pathways to phrenic motor plasticity.
急性间歇性低氧（AIH）通过脑干神经网络激活与局部（脊髓）组织缺氧引发不同的膈神经运动可塑性机制。在中度 AIH（mAIH）中，低氧血症激活颈动脉体化学感受器，（随后）激活与外周化学反射相关的脑干神经网络，包括延髓中缝背侧 5-羟色胺能神经元。膈神经运动核中 5-羟色胺的释放和受体激活随后引发膈神经长期易化（pLTF）。这种机制与组织缺氧无关，因为电刺激颈动脉窦神经可引发类似的依赖 5-羟色胺的 pLTF。与此形成鲜明对比的是，严重 AIH（sAIH）引发依赖脊髓腺苷的、不依赖 5-羟色胺的 pLTF 机制。脊髓组织缺氧本身可能是 sAIH 诱导 pLTF 的原因，因为局部组织缺氧会引发细胞外腺苷积累。因此，任何加剧脊髓组织缺氧的生理状况预计都会使平衡向腺苷能 pLTF 倾斜。然而，由于这些机制因相互交叉抑制而竞争主导地位，因此从 5-羟色胺到腺苷主导的 pLTF 的转变相当突然。任何损害脊髓循环的因素都会限制脊髓组织中的氧气供应，有利于向腺苷能机制倾斜。这种转变可能会因颈动脉去神经、自发性低血压或贫血等实验处理而产生。许多神经疾病，如脊髓损伤或中风，会损害局部循环控制，可能会调节组织氧、腺苷水平，并因此调节膈神经运动可塑性。在这篇简短的综述中，我们讨论了这样一个概念，即局部（脊髓）循环控制和/或氧输送调节了不同途径对膈神经运动可塑性的相对贡献。
