Reduced motor neuron excitability is an important contributor to weakness in a rat model of sepsis.
Reduced motor neuron excitability is an important contributor to weakness in a rat model of sepsis.
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DOI：
10.1016/j.expneurol.2016.04.020
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发表时间：
2016-08
影响因子：
5.3
通讯作者：
Rich MM
中科院分区：
文献类型：
--
作者：
Nardelli P;Vincent JA;Powers R;Cope TC;Rich MM
脓毒症触发重症监护病房获得性虚弱（ICUAW）的机制尚不清楚。我们以前确定运动单位募集困难是ICUAW的一个新的贡献者。为了研究运动单位募集不良的机制，我们使用了大鼠盲肠结扎和穿孔脓毒症模型。我们发现了在重复放电过程中α运动神经元的显著功能障碍。射击更加不稳定，而且经常断断续续。我们的数据提出了运动神经元兴奋性降低是脓毒症引起的虚弱的重要因素的可能性。在这项研究中，我们量化了运动神经元兴奋性降低的贡献，并将其幅度与肌病、神经病和神经肌肉传递失败的贡献进行了比较。我们将恒定的去极化电流脉冲（5秒）注入麻醉大鼠腰骶脊髓中α运动神经元的索马体中，以触发重复放电。响应于恒定去极化，未处理的对照大鼠中的运动神经元以稳定和连续的放电率放电，并如预期的那样产生平滑和持续的强直运动单位力。相比之下，诱导脓毒症后，运动神经元通常无法在整个5s电流注射期间维持放电，使得力产生减少。即使在放电时，脓毒症大鼠的运动神经元也不规则和不连续地放电，导致运动单位力的不规则产生。快型和慢型运动神经元的兴奋性都有类似的破坏。我们跟踪大鼠从脓毒症恢复后，以确定运动神经元兴奋性缺陷的解决的时间过程。到一周时，大鼠似乎已从脓毒症中恢复，因为它们没有竖毛并且似乎没有痛苦。运动神经元重复放电的缺陷在2周时仍然明显，尽管有所改善，但在1个月时仍然存在。我们推断，大鼠在脓毒症消退后数周内由于运动神经元兴奋性降低而出现虚弱。为了评估是否来自肌病、神经病变和神经肌肉传递缺陷的额外贡献有助于力产生的减少，我们测量了响应于肌肉神经的电刺激的全肌肉力产生。我们没有发现异常的力量产生，这将表明存在肌病，神经病变或神经肌肉传递缺陷。这些数据表明，运动神经元重复放电的中断是脓毒症诱导的大鼠虚弱的重要因素，并提高了运动神经元兴奋性降低导致脓毒症消退后持续残疾的可能性。
The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron excitability and compared its magnitude to the contributions of myopathy, neuropathy and failure of neuromuscular transmission. We injected constant depolarizing current pulses (5 sec) into the soma of alpha motor neurons in the lumbosacral spinal cord of anesthetized rats to trigger repetitive firing. In response to constant depolarization, motor neurons in untreated control rats fired at steady and continuous firing rates and generated smooth and sustained tetanic motor unit force as expected. In contrast, following induction of sepsis, motor neurons were often unable to sustain firing throughout the 5s current injection such that force production was reduced. Even when firing, motor neurons from septic rats fired erratically and discontinuously, leading to irregular production of motor unit force. Both fast and slow type motor neurons had similar disruption of excitability. We followed rats after recovery from sepsis to determine the time course of resolution of the defect in motor neuron excitability. By one week, rats appeared to have recovered from sepsis as they had no piloerection and appeared to be in no distress. The defects in motor neuron repetitive firing were still striking at 2 weeks and, although improved, were present at one month. We infer that rats suffered from weakness due to reduced motor neuron excitability for weeks after resolution of sepsis. To assess whether additional contributions from myopathy, neuropathy and defects in neuromuscular transmission contributed to the reduction in force generation, we measured whole-muscle force production in response to electrical stimulation of the muscle nerve. We found no abnormality in force generation that would suggest the presence of myopathy, neuropathy or defective neuromuscular transmission. These data suggest disruption of repetitive firing of motor neurons is an important contributor to weakness induced by sepsis in rats and raise the possibility that reduced motor neuron excitability contributes to disability that persists after resolution of sepsis.